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Review

Aspergillus oryzae as a Cell Factory: Research and Applications in Industrial Production

by
Zeao Sun
1,2,
Yijian Wu
2,
Shihua Long
2,
Sai Feng
1,2,
Xiao Jia
2,
Yan Hu
2,
Maomao Ma
2,
Jingxin Liu
2,* and
Bin Zeng
2,*
1
College of Chemistry and Chemical Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013, China
2
College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China
*
Authors to whom correspondence should be addressed.
J. Fungi 2024, 10(4), 248; https://doi.org/10.3390/jof10040248
Submission received: 8 February 2024 / Revised: 15 March 2024 / Accepted: 15 March 2024 / Published: 26 March 2024
(This article belongs to the Special Issue Filamentous Fungi as Excellent Industrial Strains: Development and Applications)
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Abstract

:
Aspergillus oryzae, a biosafe strain widely utilized in bioproduction and fermentation technology, exhibits a robust hydrolytic enzyme secretion system. Therefore, it is frequently employed as a cell factory for industrial enzyme production. Moreover, A. oryzae has the ability to synthesize various secondary metabolites, such as kojic acid and L-malic acid. Nevertheless, the complex secretion system and protein expression regulation mechanism of A. oryzae pose challenges for expressing numerous heterologous products. By leveraging synthetic biology and novel genetic engineering techniques, A. oryzae has emerged as an ideal candidate for constructing cell factories. In this review, we provide an overview of the latest advancements in the application of A. oryzae-based cell factories in industrial production. These studies suggest that metabolic engineering and optimization of protein expression regulation are key elements in realizing the widespread industrial application of A. oryzae cell factories. It is anticipated that this review will pave the way for more effective approaches and research avenues in the future implementation of A. oryzae cell factories in industrial production.

1. Introduction

Filamentous fungus, including A. oryzae, Rhizopus oryzae, etc., widely recognized as a prominent strain in the industrial sector, finds extensive applications across diverse industries, including pharmaceutical manufacturing and food processing [1,2]. A. oryzae is an important strain in the industrial application of filamentous fungi, given its long history and vast range of applications. In China and Japan, A. oryzae has been extensively employed in the food industry, particularly in the production of traditional fermented foods such as soybean paste and sake. It is also widely recognized as safe (GRAS) by the U.S. Food and Drug Administration (FDA) [3,4]. After an extended period of acclimatization, A. oryzae develops a robust system for protein secretion and post-translational modification including glucoamylase, cellulase, and protease [5,6]. Furthermore, A. oryzae exhibits robust capabilities in the degradation of various organic matter and plays a pivotal role in the biocycle. In conclusion, A. oryzae proves to be an ideal strain for establishing bio-factories that produce industrial enzymes, enabling its significant contribution to the fields of medicine, environment, and food production [7,8,9].
In 2005, Galagan et al. [10] completed the whole genome sequencing of A. oryzae, which laid the foundation for genomic research. Such research provides a basis for addressing the challenge of constructing a cell factory from A. oryzae using synthetic biological methods. In traditional industry, it exhibits the characteristics of producing multiple hydrolases, such as α-amylases, endo-proteinases, and exo-peptidases. Genome sequence analysis has revealed that A. oryzae harbors at least 500 genes with potential practical value in industrial applications [10]. Moreover, the metabolic network of filamentous fungi significantly differs from that of human and yeast cells, facilitating the discovery of novel synthetic routes for secondary metabolites. A. oryzae has a clean background of secondary metabolism synthesis and is suitable for producing multiple secondary metabolites, including kojic acid (KA), L-malic acid, and salidroside [11,12,13]. In fact, A. oryzae has been found to contain abundant numbers of secondary metabolite gene clusters, surpassing the numbers found in other sequenced species (typically around 5–15) [14,15,16]. This highlights the previously underestimated potential of A. oryzae as an industrial strain.
The main challenge in applying A. oryzae is the low level of secondary metabolites and recombinant protein expression in wild-type strains. Traditional methods, such as random mutagenesis, have been applied to increase yields of secondary metabolites in A. oryzae [17]. However, these methods suffer from the significant drawback of being inefficient in modifying low-yielding strains. Therefore, it is crucial to establish a rational and efficient breeding methodology based on genetic engineering and metabolic engineering of high-producing strains to enable the commercial application of A. oryzae. With the advancement of gene editing technology, the breeding technology of A. oryzae has undergone significant development, which is advantageous to developing high-producing cell factories. At present, it is successfully applied to genetic manipulation in A. oryzae, including the polyethylene glycol (PEG)-mediated protoplast transformation method, encompassing agrobacterium-mediated transformation, and multiplexed CRISPR/Cas9-mediated genome editing [18,19,20].
In conclusion, A. oryzae demonstrates significant potential for industrial applications and effective gene editing methods have been established. In this review, we aim to highlight recent advances in industrial application of A. oryzae research and development, with a particular focus on instances concerning cell factories, which are summarized in Figure 1.

2. Cell Factory of Producing Secondary Metabolite by A. oryzae

The field of secondary metabolite application in filamentous fungi is rapidly expanding [21]. The gene sequences for multiple Aspergilli provide a plethora of predictive information regarding production of various secondary metabolites, ranging from deadly toxins to anti-cancer drugs [22]. The notable advantage of A. oryzae is its inability to produce toxic compounds due to dysfunctional or non-expressed genes in the aflatoxin synthesis gene cluster, such as cyclopiazonic acid synthetases and non-ribosomal peptide synthetase [23,24]. In addition, A. oryzae possesses a robust metabolic flux that facilitates provision for precursors of polyketides, terpenoids, and peptides [25,26]. Therefore, using A. oryzae, we can easily determine the synthetic route for production of beneficial compounds, regardless of whether or not the metabolic is expressed heterologously. In fact, many researchers have already made significant strides in the production of secondary metabolites in A. oryzae, as shown in Table 1. These results collectively demonstrate that A. oryzae serves as an ideal foundational cell for establishing a secondary metabolite cell factory.

2.1. Metabolic Engineering of KA Production in A. oryzae

KA, a representative secondary metabolite produced by filamentous fungi, finds extensive applications in the cosmetics, pharmaceutical, and food industries. Chemically, it is a pyran-4-one with molecular formula C6H6O4, summarized in Figure 2A [38]. Using a three-step chemo-enzymatic route, Lassfolk et al. realized the preparation of KA from D-glucose via glucosone [39], as depicted in Figure 2B. However, fermentation by filamentous fungi (the producing strains include A. oryzae, Aspergillus niger) remains the primary method for KA production. The biosynthesis of KA involves complex responses. Numerous researchers have endeavored to identify the metabolic pathway of glucose conversion into KA, with Figure 3 highlighting the main routes that have received significant attention. Firstly, glucose undergoes dehydrogenation catalyzed by GDH, resulting in the formation of gluconic acid δ-lactone. Subsequently, gluconic acid can either undergo dehydrogenation to yield 3-ketogluconic acid lactone or dehydration to produce oxygenated KA. Among these pathways, 3-ketogluconic acid lactone is reduced to 3-ketoglucose, which is further dehydrated to form KA. However, the precise mechanism underlying the conversion of oxygenated KA into KA remains unknown and could be a multi-step process that might be the focus of further investigation [12].
Confirmation of the gene cluster as the foundation for constructing an efficient cell factory to produce the secondary metabolites is essential. Previous studies have identified the gene cluster and its associated genes that influence KA production in A. oryzae. The gene cluster comprises three genes, namely kojA, kojR, and kojT, which encoding FAD-dependent oxidoreductase, Zn2+2Cys6 transcriptional activator, synaptic vesicle transporter, respectively. Additionally, near the KA gene cluster, we find two genes, kap4 and kap6, that have been found to exert significant influence on KA production. Studies have elucidated their effects on KA production. Knocking out these genes resulted in a deficiency of KA production, whether one or more were knocked out, in kojA, kojR, and kojT, without remedial measure. The research revealed that overexpression of the kojR gene within the gene cluster resulted in the highest KA yield, which was 324.28% higher than the control, while exogenous KA impaired the influence of the kojR gene [12,41]. Disrupting the kap4 gene led to a lack of KA production, while disruption of kap6 repressed KA production, together with the reduced expression of kojA, kojR, and kojT. As shown in Figure 4, these findings suggest that numerous genetic regulations occur during the conversion of metabolic intermediates to direct glucose towards KA synthesis.
Apart from overexpressing the gene cluster, constructing an efficient cell factory also involves the optimal optimization of regulatory elements, such as promoter optimization, overexpression, or disruption of regulatory genes. We reviewed several beneficial studies, which are presented in Table 2. Despite only one gene being modified in these studies, the results demonstrate the relationship between regulatory genes and KA yield, and can be used as a guide for designing a cell factory. Of interest, autophagy processes, particularly autophagy of the nucleus and protein targeting to the vacuole, can influence secondary metabolite production in filamentous fungi [46]. Additionally, another study revealed that AoZip2 genes from the ZRT/IRT-like protein (ZIP) family also affect kojic acid expression, as kojic acid expression was downregulated when the AoZip2 gene was overexpressed [47]. This finding might be attributed to the responses to metal ions in kojic acid production in A. oryzae. These results provide valuable insights into building an efficient cell factory, where the overexpression and disruption of a series of genes are required to increase KA yield as part of system engineering.

2.2. Molecular Mechanism for Secondary Metabolite Secretion in A. oryzae

In A. oryzae, several secondary metabolites possess unique molecular mechanisms of secretion. However, the transportation processes involved in many of these metabolites remain unclear. Regarding the secretion of citric acid in filamentous fungi, extensive research has been conducted [53]. Initially, CtpA and YhmA play a crucial role in transporting citric acid from the mitochondria to the cytoplasm, and their transporters are localized to the mitochondrial membrane [54]. Subsequently, a dedicated transporter facilitates the transportation of citric acid from the cytoplasm to extracellular secretion. The transcription of cexA, the gene encoding this transporter, is regulated by LaeA [55]. It has been observed that overexpression of the cexA gene in A. oryzae cells enhances citric acid secretion, suggesting that cexA is a limiting factor for this process [56]. These findings highlight the importance of optimizing the secretion mechanism in A. oryzae to increase secondary metabolite yield.

3. Cell Factory for Producing Industrial Enzymes with A. oryzae

Enzymes offer several advantages in green production, including milder operating conditions, enhanced product specificity, efficient resource utilization, and pollution reduction [57]. As green production becomes more prevalent, the global industrial enzymes market is expanding at a rapid pace, estimated to be valued at USD 7.42 billion in 2023 [58]. Demand for these products in the animal feed, pharmaceutical, and nutraceutical sectors is expected to experience significant growth, driven by the expansion of meat production and the pharmaceutical industry. In 2023, the microorganisms segment dominated the industrial enzyme market, accounting for the highest share at 85.49%, primarily due to their low production cost and easy availability. Among the various characteristics of A. oryzae, as a production strain for fermented food, one of the most important is its ability to produce significant amounts of extracellular hydrolytic enzymes, such as amylolytic and proteolytic enzymes [59,60]. Furthermore, compared with Escherichia coli and Saccharomyces cerevisiae, A. oryzae is a superior host for expressing proteins with intricate structures, owing to its stronger posttranslational modification function. Therefore, A. oryzae is well suited for the production of industrial enzymes. Table 3 lists many various relevant studies related to production of industrial enzymes in A. oryzae. In general, A. oryzae has a wide range of applications for industrial enzyme production. However, due to its inefficiency, heterogeneous expression of proteins in A. oryzae is a challenging event, which may be related to complicated secretory pathways.

3.1. α-Amylase Production in A. oryzae

Amylases, which were first identified in the eighteenth century and are found in bacteria, fungi, animals, and plants, are among the enzymes initially used in industrial production [76]. Microbial-based commercial production of amylases accounts for approximately 30% of the global enzyme market [77]. α-amylase is a prominent secretory protein in A. oryzae and finds extensive application in industrial enzymes [78]. Understanding of its regulatory mechanisms and secretory pathway is the key to increasing its production.
The expression of α-amylase genes in A. oryzae is induced by starch and malto-oligosaccharides. The gene-inducible expression is regulated by AmyR, one of the fungal-specific Zn(II)2Cys6-type transcription factors [78]. The AmyR gene is usually constitutively expressed and localizes in the cytoplasm. However, upon addition of isomaltose to the medium, AmyR is rapidly transferred into the nucleus [79]. In contrast to A. nidulans, c-terminal truncation of AmyR in A. oryzae leads to the loss of its function, indicating species-specific differences in AmyR among Aspergillus species. In multicellular organisms, the regulation of gene expression involves key factors known as morphogens that play a role in organizing gene expression [80]. However, filamentous fungal cells are highly polarized, and generally the nucleus is at some distance from the tip of the hypha, which distinguishes A. oryzae from others [81,82]. Furthermore, the regulation of the cell cycle in Aspergillus species is synchronized, which differs from most multicellular systems [83]. Consequently, the mechanism of AmyR activation in A. oryzae is more complex. Maltose is incorporated by the maltose permease MalP and converted to isomaltose by the transglycosylation activity of the intracellular α-glucosidase MalT [84]. This mechanism may have a beneficial effect on increasing amylase production. The α-amylase (amyB) gene promoter also is commonly used for high-level expression of heterologous genes in A. oryzae [59].

3.2. Molecular Mechanism for Protein Secretion in A. oryzae

In the A. oryzae genome, there are 135 genes predicted as secretory protease by signal peptide, including amylase genes [85]. Solid-state culture is a commonly used industrial method to cultivate A. oryzae cells to produce industrial enzymes, as secretory proteins are produced to a greater extent in solid-state culture compared with submerged culture [86]. However, there are certain proteins that are not secreted in solid-state culture, unlike submerged culture, such as the glucoamylase-encoding gene glaB [87]. These findings suggest that there is a molecular mechanism governing protein secretion in A. oryzae.
The secreted protein contains a signal peptide at the N-terminus, which initially targets it to the endoplasmic reticulum (ER). It is then transported from the ER to the plasma membrane via vesicles through the Golgi apparatus before finally being secreted outside of the cell. During its passage through the ER and Golgi, secreted proteins undergo modifications through the addition of N- and/or O-glycan chains, which serve functions such as protein stabilization and localization. The mechanism of N-glycosylation is highly conserved in filamentous fungi. Within the ER lumen, secreted proteins undergo the calnexin/calreticulin cycle prior to transport to the Golgi. The Glc3Man9GlcNA2 moeity is attached to the Asn residue of the glycoprotein, which is then further processed by glucosidases I and II to remove the Glc moiety [88]. The remaining individual GlcNAc moiety on the secreted expressed protein is important for maintaining protein structure and function, and it affects enzyme activity [89]. In A. oryzae, N-glcNAc-modified proteins are produced extracellularly through the expression of endo-β-N-acetylglucosaminidase (ENGase) located on the Golgi membrane [90]. In addition, the fluorescence localization signals show that secreted expressed proteins are mainly secreted from the hyphal tip in A. oryzae [91]. In this process, the actin and microtubule cytoskeletons are indispensable. There is septum-directed secretion in A. oryzae [92]. This process is illustrated in Figure 5.

4. Cell Factory of Utilized Organic-Rich Waste by A. oryzae

In modern society, a significant amount of organic-rich waste is generated, posing harmful effects on the environment. The green production standard advocates for the appropriate treatment and recycling of organic-rich waste [93]. Utilizing cell factories to produce valuable commodities based on this waste is an effective method of waste treatment [94,95]. Current research suggests that the primary products generated by cell factories include biosurfactants, enzyme preparations, single-cell proteins, and polyols [96,97,98]. Additionally, certain types of organic-rich waste can be utilized as a suitable growth medium for specialized strains (including genetically modified and naturally screened strains), thereby inducing the synthesis of relevant secondary metabolites. This use of organic-rich waste is powerful for sustainable development of the circular bioeconomy. In Figure 6, we summarize some possible products and the strengths and weaknesses of the cell factory to treat organic-rich waste. The primary challenge currently faced by cell factory relates to identifying microbial strains that exhibit a remarkable capacity for efficient utilization of organic-rich waste, as well as implementing effective metabolic engineering strategies to optimize performance. A. oryzae possesses an efficient hydrolase system, which includes phytases, β-glucosidases, and other enzymes [99,100,101,102]. Furthermore, A. oryzae is an ideal candidate for constructing a cell factory due to its ability to withstand high osmolality and other challenging environments. Extensive research in this field has yielded numerous intriguing and valuable discoveries, highlighting the significance and potential for further exploration of A. oryzae.

4.1. Cell Factories for Processing Food Waste

The food processing industry represents one of the primary sources of organic-rich waste [103]. The composition of food waste is complex, which makes it difficult to manage. Waste cooking oil (WCO) poses a challenge in food waste treatment due to its toxic effects on certain microorganisms [104]. Figure 7 illustrates the principal metabolic pathways employed in a commonly used model cell factory for studying the degradation of WCO. The metabolic pathway of WCO within an organism is closely linked with intracellular lipid metabolism and effectively bypasses the tricarboxylic acid cycle. For instance, Hui Huang et al. [105] demonstrated the beneficial effects of the thiolytic enzyme gene in the utilization of WCO, as observed during the study of ergosterol. Another study utilized A. oryzae to produce single cell protein from waste-derived volatile fatty acids (VFAs) and achieved a biomass yield of 0.26 g dry biomass/g VFAsfed [106]. Furthermore, the presence of cooking oil exhibited a significant influence on biomass growth. Muhammad Tahir Nazir et al. analyzed the biomass obtained from A. oryzae for protein, fat, and alkali-insoluble material, revealing a biomass growth of 16 g/L with the addition of oil compared with 4 g/L without oil [107].
In addition to WCO, other wastes generated during food production can be digested by A. oryzae. Natsumi Iwamoto et al. found that abalone viscera fermented by A. oryzae 001 had an inhibitory effect on blood pressure elevation, possibly due to the isolation of L-m-tyrosine, a unique substance in fermented abalone viscera, which was identified as a single ACE-inhibitory amino acid for the first time [108]. Brewer’s spent grain (BSG) is the main solid by-product of the brewing sector. Research has shown that submerged cultivation of BSG with A. oryzae can significantly enhance the protein content, with the highest increase observed at 34.6% (from 22.6%), and a concurrent decrease in the content of polysaccharides by up to approximately 50% [109]. Barley bran (BB) is a by-product of the milling process. Solid substrate fermentation (SSF) of BB was performed with A. oryzae for 7 days, resulting in an improvement in the bioactive compounds of BB, including increased levels of ascorbic acid (107.15 µg/g), gallic acid (405.5 µg/g), catechin (88.3 µg/g), vanillin (40.89 µg/g), and resorcinol (20.7 µg/g) [110]. Furthermore, Ikram-Ul-Haq et al., using a soya bean meal medium, conducted submerged fermentation with A. oryzae to produce β-galactosidase, with a maximum productivity of 112.34 ± 0.23 U/mL/min [111]. In general, utilizing food waste to derive bioactive molecules through A. oryzae is a practical approach.
Moreover, intensive research has demonstrated that food waste can be utilized for production of biofuels, such as ethanol and lipids for biodiesel. A. oryzae, the strain used for sake production, is an ideal candidate for constructing a cell factory. Joanna Kawarygielska et al. reported A. oryzae final product yields ranging from 0.29 to 0.32 g EtOH/g and 0.20 to 0.22 g biomass/g bread waste, on the second fermentation [112]. Abdullah Bilal Ozturk et al. conducted experiments to test the production of bio-butanol through fermentation of Japanese steamed rice using A. oryzae and Clostridium acetobutylicum, and the output was (10.91 ± 0.16) g/L [113].

4.2. Cell Factory for Processing Agricultural Waste

Lignocellulose constitutes the primary component of waste generated in agricultural production, such as corn cobs, straw chaff, etc. [114]. Additionally, lignocellulosic biomass serves as a crucial raw material for extracting bio-based fuels and other value-added products, including organic acids, fructans, phenols, mono-pentose/oligosaccharides, and hexose [115,116,117]. Microbial enzymatic saccharification of lignocellulose represents an effective approach for sustainable utilization of this resource [118,119]. A. oryzae, with its extracellular cellulase activity, emerges as an ideal strain for constructing a cell factory to process agricultural waste [94,120].
Alberto Robazza et al. utilized pyrolysis waste derived from lignocellulose as a culture substrate for L-malic acid production through inoculation of A. oryzae, achieving yields of up to 0.17 mM/mM [121]. Apart from malic acid, organic acids found in plants are also popular regenerative products. Ignacio Cabezudo et al. employed A. oryzae for gallic acid production, utilizing soybean hull and grape pomace as supporting substrates, resulting in the production of 0.36 g of gallic acid per gram of tannic acid and 7.2 g/L of fermentation medium after 72 h of incubation [69]. Moreover, lignocellulosic biomass treated with A. oryzae is commonly used in animal feed. A study was conducted to valorize this agricultural waste into alternative ruminant feed using exogenous fibrolytic enzymes (EFE) through fermentation of a mixed culture of Aspergillus strains [122].

5. Discussion and Conclusions

The global market demand for biological resources, such as secondary metabolites and industrial enzymes, continues to increase with the expansion of the pharmaceutical and healthcare markets. To address this, the use of cell factories built through synthetic biology has emerged as an effective solution for achieving green production of these products. As an organism with biosafety characteristics, A. oryzae possesses abundant gene resources for secondary metabolite synthesis and an efficient protease expression system, making it an ideal chassis organism for constructing cell factories. Research on utilizing A. oryzae to construct cell factories for industrial product production is gaining momentum.
Metabolic engineering strategies and synthetic biology tools have the potential to significantly enhance the performance of A. oryzae, encompassing synthesis capacity, growth performance, and stress resilience [123,124]. Despite the sequencing of the genomic information of A. oryzae, the metabolic pathways of numerous secondary metabolites remain elusive, presenting a major challenge in related research. Furthermore, the secretion pathways of secondary metabolites in A. oryzae have not been extensively characterized, thereby limiting the production of these metabolites. Constructing cell factories can be a promising approach to address these challenges.
Considering its exceptional protein secretion system and post-translational modification pathway, A. oryzae is considered a promising candidate for a protein cell factory [125]. Up to now, our research has focused on investigating the secretory expression system of proteins in A. oryzae, leading to successful high expression of numerous homologous proteins [126]. Nevertheless, limited knowledge about the regulation of heterologous protein expression in A. oryzae and the relatively low efficiency of such expression currently hinder its industrial implementation [127]. With advancements in proteomics and the utilization of novel gene editing technologies in A. oryzae, we are optimistic about achieving efficient expression of heterologous proteins in the A. oryzae cell factory [19,128].

6. Expectations

As a biosafe strain, A. oryzae possesses a highly efficient secondary metabolite synthesis pathway and protein secretion expression system. It has found extensive utilization in traditional industries, particularly in food production. Moreover, through the integration of proteomics and genetic engineering techniques, A. oryzae has emerged as an optimal candidate for constructing cell factories. Therefore, to facilitate the wider industrial application of the A. oryzae cell factory, comprehensive studies on its secretion system and protein expression regulation mechanism are of utmost importance.

Author Contributions

Conceptualization, Z.S. and B.Z.; methodology, Z.S.; software, Y.W.; validation, Z.S., S.F. and Y.H.; formal analysis, S.L.; investigation, Y.W.; resources, B.Z.; data curation, X.J.; writing—original draft preparation, Z.S.; writing—review and editing, Z.S.; visualization, S.L.; supervision, M.M.; project administration, B.Z. and J.L.; funding acquisition, B.Z. and J.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Natural Science Foundation of Top Talent of SZTU (grant no. GDRC202118), the National Natural Science Foundation of China (32200606), the Key Special Projects of the National Key Research and Development Plan (2021YFA1301302), Self-made Experimental Instruments and Equipment Project of Shenzhen Technology University (JSZZ202301021), Multiparameter detection analysis Real-time linkage control fermentation system development (20231064010150), Self-made Experimental Instruments and Equipment Project of Shenzhen Technology University (JSZZ202301022).

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Jo, C.; Zhang, J.; Tam, J.M.; Church, G.M.; Khalil, A.S.; Segré, D.; Tang, T.C. Unlocking the magic in mycelium: Using synthetic biology to optimize filamentous fungi for biomanufacturing and sustainability. Mater. Today Bio 2023, 19, 100560. [Google Scholar] [CrossRef]
  2. Ding, Q.; Ye, C. Microbial cell factories based on filamentous bacteria, yeasts, and fungi. Microb. Cell Factories 2023, 22, 20. [Google Scholar] [CrossRef]
  3. Lambré, C.; Baviera, J.M.B.; Bolognesi, C.; Cocconcelli, P.S.; Crebelli, R.; Gott, D.M.; Grob, K.; Lampi, E.; Mengelers, M.; Mortensen, A.; et al. Safety evaluation of the food enzyme phospholipase A1 from the genetically modified Aspergillus oryzae strain NZYM-LJ. EFSA J. 2022, 20, 7381. [Google Scholar] [CrossRef]
  4. Frisvad, J.C.; Møller, L.L.H.; Larsen, T.O.; Kumar, R.; Arnau, J. Safety of the fungal workhorses of industrial biotechnology: Update on the mycotoxin and secondary metabolite potential of Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei. Appl. Microbiol. Biotechnol. 2018, 102, 9481–9515. [Google Scholar] [CrossRef]
  5. Saqib, A.; Rashid, M.H. Random mutagenesis of koji (Aspergillus oryzae) to enhance the catalytic efficiency and thermostability of glucoamylase. Pak. J. Bot. 2023, 55, 1923–1929. [Google Scholar] [CrossRef] [PubMed]
  6. Chen, C.F.; Hou, S.; Wu, C.Z.; Cao, Y.; Tong, X.; Chen, Y.J. Improving protein utilization and fermentation quality of soy sauce by adding protease. J. Food Compos. Anal. 2023, 121, 105399. [Google Scholar] [CrossRef]
  7. Qiu, S.K.; Liu, Q.C.; Yuan, Y.; Zhou, H.; Zeng, B. Aspergillus oryzae accelerates the conversion of ergosterol to ergosterol peroxide by efficiently utilizing cholesterol. Front. Genet. 2022, 13, 984343. [Google Scholar] [CrossRef] [PubMed]
  8. Nomura, R.; Tsuzuki, S.; Kojima, T.; Nagasawa, M.; Sato, Y.; Uefune, M.; Baba, Y.; Hayashi, T.; Nakano, H.; Kato, M.; et al. Administration of Aspergillus oryzae suppresses DSS-induced colitis. Food Chem. Mol. Sci. 2022, 4, 100063. [Google Scholar] [CrossRef] [PubMed]
  9. Li, Q.; Lu, J.; Zhang, G.; Liu, S.; Zhou, J.; Du, G.; Chen, J. Recent advances in the development of Aspergillus for protein production. Bioresour. Technol. 2022, 348, 126768. [Google Scholar] [CrossRef] [PubMed]
  10. Galagan, J.E.; Calvo, S.E.; Cuomo, C.; Ma, L.J.; Wortman, J.R.; Batzoglou, S.; Lee, S.I.; Bastürkmen, M.; Spevak, C.C.; Clutterbuck, J.; et al. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 2005, 438, 1105–1115. [Google Scholar] [CrossRef] [PubMed]
  11. Zuo, H.Y.; Ji, L.H.; Pan, J.Y.; Chen, X.L.; Gao, C.; Liu, J.; Wei, W.Q.; Wu, J.; Song, W.; Liu, L.M. Engineering growth phenotypes of Aspergillus oryzae for L-malate production. Bioresour. Bioprocess. 2023, 10, 25. [Google Scholar] [CrossRef]
  12. Zhang, X.M.; Guo, R.; Bi, F.T.; Chen, Y.; Xue, X.L.; Wang, D.P. Overexpression of kojR and the entire koj gene cluster affect the kojic acid synthesis in Aspergillus oryzae 3.042. Gene 2024, 892, 147852. [Google Scholar] [CrossRef]
  13. Yang, R.; Wang, Y.; Zhao, X.; Tong, Z.; Zhu, Q.; He, X.; Wang, Z.; Luo, H.; Fang, F. A facile and efficient synthesis approach of salidroside esters by whole-cell biocatalysts in organic solvents. Front. Bioeng. Biotechnol. 2022, 10, 1051117. [Google Scholar] [CrossRef]
  14. Umemura, M.; Koyama, Y.; Takeda, I.; Hagiwara, H.; Ikegami, T.; Koike, H.; Machida, M. Fine De Novo Sequencing of a Fungal Genome Using only SOLiD Short Read Data: Verification on Aspergillus oryzae RIB40. PLoS ONE 2013, 8, e63673. [Google Scholar] [CrossRef]
  15. Inglis, D.O.; Binkley, J.; Skrzypek, M.S.; Arnaud, M.B.; Cerqueira, G.C.; Shah, P.; Wymore, F.; Wortman, J.R.; Sherlock, G. Comprehensive annotation of secondary metabolite biosynthetic genes and gene clusters of Aspergillus nidulans, A. fumigatus, A. niger and A. oryzae. BMC Microbiol. 2013, 13, 91. [Google Scholar] [CrossRef] [PubMed]
  16. Sato, A.; Oshima, K.; Noguchi, H.; Ogawa, M.; Takahashi, T.; Oguma, T.; Koyama, Y.; Itoh, T.; Hattori, M.; Hanya, Y. Draft Genome Sequencing and Comparative Analysis of Aspergillus sojae NBRC4239. DNA Res. 2011, 18, 165–176. [Google Scholar] [CrossRef] [PubMed]
  17. Suryadi, H.; Irianti, M.I.; Septiarini, T.H. Methods of Random Mutagenesis of Aspergillus Strain for Increasing Kojic Acid Production. Curr. Pharm. Biotechnol. 2022, 23, 486–494. [Google Scholar] [CrossRef]
  18. Nodvig, C.S.; Nielsen, J.B.; Kogle, M.E.; Mortensen, U.H. A CRISPR-Cas9 System for Genetic Engineering of Filamentous Fungi. PLoS ONE 2015, 10, e0133085. [Google Scholar] [CrossRef] [PubMed]
  19. Li, Q.; Lu, J.; Zhang, G.; Zhou, J.; Li, J.; Du, G.; Chen, J. CRISPR/Cas9-Mediated Multiplexed Genome Editing in Aspergillus oryzae. J. Fungi 2023, 9, 109. [Google Scholar] [CrossRef] [PubMed]
  20. Katayama, T.; Maruyama, J.-i. CRISPR/Cpf1-mediated mutagenesis and gene deletion in industrial filamentous fungi Aspergillus oryzae and Aspergillus sojae. J. Biosci. Bioeng. 2022, 133, 353–361. [Google Scholar] [CrossRef]
  21. Kumar, V.; Ahluwalia, V.; Saran, S.; Kumar, J.; Patel, A.K.; Singhania, R.R. Recent developments on solid-state fermentation for production of microbial secondary metabolites: Challenges and solutions. Bioresour. Technol. 2021, 323, 124566. [Google Scholar] [CrossRef]
  22. Mushtaq, S.; Abbasi, B.H.; Uzair, B.; Abbasi, R. Natural products as reservoirs of novel therapeutic agents. EXCLI J. 2018, 17, 420–451. [Google Scholar]
  23. Seshime, Y.; Juvvadi, P.R.; Tokuoka, M.; Koyama, Y.; Kitamoto, K.; Ebizuka, Y.; Fujii, I. Functional expression of the Aspergillus flavus PKS-NRPS hybrid CpaA involved in the biosynthesis of cyclopiazonic acid. Bioorganic Med. Chem. Lett. 2009, 19, 3288–3292. [Google Scholar] [CrossRef] [PubMed]
  24. Panchanawaporn, S.; Chutrakul, C.; Jeennor, S.; Anantayanon, J.; Rattanaphan, N.; Laoteng, K. Potential of Aspergillus oryzae as a biosynthetic platform for indigoidine, a non-ribosomal peptide pigment with antioxidant activity. PLoS ONE 2022, 17. [Google Scholar] [CrossRef]
  25. Petitgonnet, C.; Klein, G.L.; Roullier-Gall, C.; Schmitt-Kopplin, P.; Quintanilla-Casas, B.; Vichi, S.; Julien-David, D.; Alexandre, H. Influence of cell-cell contact between L. thermotolerans and S. cerevisiae on yeast interactions and the exo-metabolome. Food Microbiol. 2019, 83, 122–133. [Google Scholar] [CrossRef] [PubMed]
  26. Awakawa, T.; Abe, I. Reconstitution of Polyketide-Derived Meroterpenoid Biosynthetic Pathway in Aspergillus oryzae. J. Fungi 2021, 7, 486. [Google Scholar] [CrossRef] [PubMed]
  27. Kan, E.; Tomita, H.; Katsuyama, Y.; Maruyama, J.-I.; Koyama, Y.; Ohnishi, Y. Discovery of the 2,4′-Dihydroxy-3′-methoxypropiophenone Biosynthesis Genes in Aspergillus oryzae. ChemBioChem 2021, 22, 203–211. [Google Scholar] [CrossRef]
  28. Orfali, R.; Perveen, S.; Khan, M.F.; Ahmed, A.F.; Wadaan, M.A.; Al-Taweel, A.M.; Alqahtani, A.S.; Nasr, F.A.; Tabassum, S.; Luciano, P.; et al. Antiproliferative Illudalane Sesquiterpenes from the Marine Sediment Ascomycete Aspergillus oryzae. Mar. Drugs 2021, 19, 333. [Google Scholar] [CrossRef]
  29. Zhu, K.; Liu, X.; Qi, X.; Liu, Q.; Wang, B.; Sun, W.; Pan, B. Acaricidal activity of bioactive compounds isolated from Aspergillus oryzae against poultry red mites, Dermanyssus gallinae (Acari: Dermanyssidae). Vet. Parasitol. 2023, 320, 109983. [Google Scholar] [CrossRef]
  30. Han, H.; Yu, C.; Qi, J.; Wang, P.; Zhao, P.; Gong, W.; Xie, C.; Xia, X.; Liu, C. High-efficient production of mushroom polyketide compounds in a platform host Aspergillus oryzae. Microb. Cell Factories 2023, 22, 60. [Google Scholar] [CrossRef]
  31. Jiao, J.; Fu, J.-X.; Gai, Q.-Y.; He, X.-J.; Feng, X.; Cao, R.-Z.; Fu, Y.-J. The enhanced production and secretion of high-value cajaninstilbene acid and flavonoid aglycones in Cajanus cajan (Linn.) Millsp. cell suspension cultures elicited by Aspergillus oryzae Y-29. Process Biochem. 2023, 130, 127–137. [Google Scholar] [CrossRef]
  32. Kövilein, A.; Zadravec, L.; Hohmann, S.; Umpfenbach, J.; Ochsenreither, K. Effect of process mode, nitrogen source and temperature on L-malic acid production with Aspergillus oryzae DSM 1863 using acetate as carbon source. Front. Bioeng. Biotechnol. 2022, 10, 1033777. [Google Scholar] [CrossRef] [PubMed]
  33. Schmitt, V.; Derenbach, L.; Ochsenreither, K. Enhanced l-Malic Acid Production by Aspergillus oryzae DSM 1863 Using Repeated-Batch Cultivation. Front. Bioeng. Biotechnol. 2022, 9, 760500. [Google Scholar] [CrossRef] [PubMed]
  34. Kövilein, A.; Aschmann, V.; Hohmann, S.; Ochsenreither, K. Immobilization of Aspergillus oryzae DSM 1863 for l-Malic Acid Production. Fermentation 2022, 8, 26. [Google Scholar] [CrossRef]
  35. Ji, L.; Wang, J.; Luo, Q.; Ding, Q.; Tang, W.; Chen, X.; Liu, L. Enhancing L-malate production of Aspergillus oryzae by nitrogen regulation strategy. Appl. Microbiol. Biotechnol. 2021, 105, 3101–3113. [Google Scholar] [CrossRef] [PubMed]
  36. Mahmoud, G.A.E.; Zohri, A.N.A. Amedment stable kojic acid produced by non-toxinogenic Aspergillus oryzae using five levels central composite design of response surface methodology. J. Microbiol. Biotechnol. Food Sci. 2021, 10, e2683. [Google Scholar] [CrossRef]
  37. Li, J.S.; Chew, Y.M.; Lin, M.C.; Lau, Y.Q.; Chen, C.S. Enhanced glucosamine production from Aspergillus oryzae NCH-42 via acidic stress under submerged fermentation. Cyta-J. Food 2021, 19, 614–624. [Google Scholar] [CrossRef]
  38. Sharma, S.; Singh, S.; Sarma, S.J. Challenges and advancements in bioprocess intensification of fungal secondary metabolite: Kojic acid. World J. Microbiol. Biotechnol. 2023, 39, 140. [Google Scholar] [CrossRef]
  39. Lassfolk, R.; Suonpää, A.; Birikh, K.; Leino, R. Chemo-enzymatic three-step conversion of glucose to kojic acid. Chem. Commun. 2019, 55, 14737–14740. [Google Scholar] [CrossRef]
  40. Troiano, D.; Orsat, V.; Dumont, M.J. Status of filamentous fungi in integrated biorefineries. Renew. Sustain. Energy Rev. 2020, 117, 109472. [Google Scholar] [CrossRef]
  41. Chang, P.-K.; Scharfenstein, L.L.; Mahoney, N.; Kong, Q. Kojic Acid Gene Clusters and the Transcriptional Activation Mechanism of Aspergillus flavus KojR on Expression of Clustered Genes. J. Fungi 2023, 9, 259. [Google Scholar] [CrossRef]
  42. Marui, J.; Yamane, N.; Ohashi-Kunihiro, S.; Ando, T.; Terabayashi, Y.; Sano, M.; Ohashi, S.; Ohshima, E.; Tachibana, K.; Higa, Y.; et al. Kojic acid biosynthesis in Aspergillus oryzae is regulated by a Zn(II)2Cys6 transcriptional activator and induced by kojic acid at the transcriptional level. J. Biosci. Bioeng. 2011, 112, 40–43. [Google Scholar] [CrossRef]
  43. Arakawa, G.-y.; Kudo, H.; Yanase, A.; Eguchi, Y.; Kodama, H.; Ogawa, M.; Koyama, Y.; Shindo, H.; Hosaka, M.; Tokuoka, M. A unique Zn(II)2-Cys6-type protein, KpeA, is involved in secondary metabolism and conidiation in Aspergillus oryzae. Fungal Genet. Biol. 2019, 127, 35–44. [Google Scholar] [CrossRef] [PubMed]
  44. Chen, T.; Chen, Z.; Li, Y.; Zeng, B.; Zhang, Z. A Novel Major Facilitator Superfamily Transporter Gene Aokap4 near the Kojic Acid Gene Cluster Is Involved in Growth and Kojic Acid Production in Aspergillus oryzae. J. Fungi 2022, 8, 885. [Google Scholar] [CrossRef]
  45. Chen, Z.; Chen, T.; Wang, H.; Jiang, C.; Liu, Y.; Wu, X.; Li, Y.; Zeng, B.; Zhang, Z. Disruption of Aokap6 near the kojic acid gene cluster affects the growth and kojic acid production in Aspergillus oryzae. World J. Microbiol. Biotechnol. 2022, 38, 175. [Google Scholar] [CrossRef] [PubMed]
  46. Chen, J.; Arioka, M. Autophagy deficiency boosts the production of kojic acid in the filamentous fungus Aspergillus oryzae. Biosci. Biotechnol. Biochem. 2021, 85, 2429–2433. [Google Scholar] [CrossRef]
  47. Zhang, Z.; Fan, J.; Long, C.; He, B.; Hu, Z.; Jiang, C.; Li, Y.; Ma, L.; Wen, J.; Zou, X.; et al. Identification and characterization of the ZRT, IRT-like protein (ZIP) family genes reveal their involvement in growth and kojic acid production in Aspergillus oryzae. J. Ind. Microbiol. Biotechnol. 2019, 46, 1769–1780. [Google Scholar] [CrossRef]
  48. Kudo, H.; Arakawa, G.-y.; Shirai, S.; Ogawa, M.; Shindo, H.; Hosaka, M.; Tokuoka, M. New role of a histone chaperone, HirA: Involvement in kojic acid production associated with culture conditions in Aspergillus oryzae. J. Biosci. Bioeng. 2022, 133, 235–242. [Google Scholar] [CrossRef]
  49. Li, Y.; Zhang, H.; Chen, Z.; Fan, J.; Chen, T.; Xiao, Y.; Jie, J.; Zeng, B.; Zhang, Z. Overexpression of a novel gene Aokap2 affects the growth and kojic acid production in Aspergillus oryzae. Mol. Biol. Rep. 2022, 49, 2745–2754. [Google Scholar] [CrossRef] [PubMed]
  50. Li, Y.; Chen, Z.; Zhang, F.; Chen, T.; Fan, J.; Deng, X.; Lei, X.; Zeng, B.; Zhang, Z. The C2H2-type zinc-finger regulator AoKap5 is required for the growth and kojic acid synthesis in Aspergillus oryzae. Fungal Genet. Biol. 2023, 167, 103813. [Google Scholar] [CrossRef] [PubMed]
  51. Li, Y.; Zhang, H.; Chen, Z.; Fan, J.; Chen, T.; Zeng, B.; Zhang, Z. Identification and characterization of a novel gene Aokap1 involved in growth and kojic acid synthesis in Aspergillus oryzae. Arch. Microbiol. 2021, 204, 67. [Google Scholar] [CrossRef]
  52. Chen, Z.; Chen, T.; Zhang, H.; Li, Y.; Fan, J.; Yao, L.; Zeng, B.; Zhang, Z. Functional role of a novel zinc finger protein, AoZFA, in growth and kojic acid synthesis in Aspergillus oryzae. Appl. Environ. Microbiol. 2023, 89, e00909–e00923. [Google Scholar] [CrossRef] [PubMed]
  53. Futagami, T.; Mori, K.; Wada, S.; Ida, H.; Kajiwara, Y.; Takashita, H.; Tashiro, K.; Yamada, O.; Omori, T.; Kuhara, S.; et al. Transcriptomic Analysis of Temperature Responses of Aspergillus kawachii during Barley Koji Production. Appl. Environ. Microbiol. 2015, 81, 1353–1363. [Google Scholar] [CrossRef]
  54. Kadooka, C.; Izumitsu, K.; Onoue, M.; Okutsu, K.; Yoshizaki, Y.; Takamine, K.; Goto, M.; Tamaki, H.; Futagami, T. Mitochondrial Citrate Transporters CtpA and YhmA Are Required for Extracellular Citric Acid Accumulation and Contribute to Cytosolic Acetyl Coenzyme A Generation in Aspergillus luchuensis mut. kawachii. Appl. Environ. Microbiol. 2019, 85, e03136-18. [Google Scholar] [CrossRef] [PubMed]
  55. Kadooka, C.; Nakamura, E.; Mori, K.; Okutsu, K.; Yoshizaki, Y.; Takamine, K.; Goto, M.; Tamaki, H.; Futagami, T. LaeA Controls Citric Acid Production through Regulation of the Citrate Exporter-Encoding cexA Gene in Aspergillus luchuensis mut. kawachii. Appl. Environ. Microbiol. 2020, 86, e01950-19. [Google Scholar] [CrossRef]
  56. Nakamura, E.; Kadooka, C.; Okutsu, K.; Yoshizaki, Y.; Takamine, K.; Goto, M.; Tamaki, H.; Futagami, T. Citrate exporter enhances both extracellular and intracellular citric acid accumulation in the koji fungi Aspergillus luchuensis mut. kawachii and Aspergillus oryzae. J. Biosci. Bioeng. 2021, 131, 68–76. [Google Scholar] [CrossRef] [PubMed]
  57. Srivastava, B.; Khatri, M.; Singh, G.; Arya, S.K. Microbial keratinases: An overview of biochemical characterization and its eco-friendly approach for industrial applications. J. Clean. Prod. 2020, 252, 119847. [Google Scholar] [CrossRef]
  58. Sujitha, P.; Shanthi, C. Importance of enzyme specificity and stability for the application of proteases in greener industrial processing- a review. J. Clean. Prod. 2023, 425, 138915. [Google Scholar] [CrossRef]
  59. Jin, F.-J.; Hu, S.; Wang, B.-T.; Jin, L. Advances in Genetic Engineering Technology and Its Application in the Industrial Fungus Aspergillus oryzae. Front. Microbiol. 2021, 12, 644404. [Google Scholar] [CrossRef]
  60. Oikawa, H. Reconstitution of biosynthetic machinery of fungal natural products in heterologous hosts. Biosci. Biotechnol. Biochem. 2020, 84, 433–444. [Google Scholar] [CrossRef]
  61. Atalla, S.M.M.; Ahmed, N.E.; Awad, H.M.; El Gamal, N.G.; El Shamy, A.R. Statistical optimization of xylanase production, using different agricultural wastes by Aspergillus oryzae MN894021, as a biological control of faba bean root diseases. Egypt. J. Biol. Pest Control 2020, 30, 125. [Google Scholar] [CrossRef]
  62. de Carvalho, M.S.; de Menezes, L.H.S.; Pimentel, A.B.; Costa, F.S.; Oliveira, P.C.; dos Santos, M.M.O.; de Carvalho Tavares, I.M.; Irfan, M.; Bilal, M.; Dias, J.C.T.; et al. Application of Chemometric Methods for the Optimization Secretion of Xylanase by Aspergillus oryzae in Solid State Fermentation and Its Application in the Saccharification of Agro-industrial Waste. Waste Biomass Valori 2023, 14, 3183–3193. [Google Scholar] [CrossRef]
  63. Pragya; Sharma, K.K.; Singh, B. Phytase from Aspergillus oryzae SBS50: Biocatalytic reduction of anti-nutritional factor and exhibiting vanadium-dependent haloperoxidase activity. Biocatal. Agric. Biotechnol. 2023, 52, 102840. [Google Scholar] [CrossRef]
  64. Michel, M.R.; Gallegos, A.C.F.; Villarreal-Morales, S.L.; Aguilar-Zárate, P.; Aguilar, C.N.; Riutort, M.; Rodríguez-Herrera, R. Fructosyltransferase production by Aspergillus oryzae BM-DIA using solid-state fermentation and the properties of its nucleotide and protein sequences. Folia Microbiol. 2021, 66, 469–481. [Google Scholar] [CrossRef]
  65. Balakrishnan, M.; Jeevarathinam, G.; Kumar, S.K.S.; Muniraj, I.; Uthandi, S. Optimization and scale-up of α-amylase production by Aspergillus oryzae using solid-state fermentation of edible oil cakes. BMC Biotechnol. 2021, 21, 33. [Google Scholar] [CrossRef]
  66. Braia, M.; Cabezudo, I.; Barrera, V.L.; Anselmi, P.; Meini, M.-R.; Romanini, D. An optimization approach to the bioconversion of flour mill waste to α-amylase enzyme by Aspergillus oryzae. Process Biochem. 2021, 111, 102–108. [Google Scholar] [CrossRef]
  67. Han, S.; Pan, L.; Zeng, W.; Yang, L.; Yang, D.; Chen, G.; Liang, Z. Improved production of fructooligosaccharides (FOS) using a mutant strain of Aspergillus oryzae S719 overexpressing β-fructofuranosidase (FTase) genes. LWT 2021, 146, 111346. [Google Scholar] [CrossRef]
  68. Han, S.; Ye, T.; Leng, S.; Pan, L.; Zeng, W.; Chen, G.; Liang, Z. Purification and biochemical characteristics of a novel fructosyltransferase with a high FOS transfructosylation activity from Aspergillus oryzae S719. Protein Expr. Purif. 2020, 167, 105549. [Google Scholar] [CrossRef] [PubMed]
  69. Cabezudo, I.; Galetto, C.S.; Romanini, D.; Furlán, R.L.E.; Meini, M.R. Production of gallic acid and relevant enzymes by Aspergillus niger and Aspergillus oryzae in solid-state fermentation of soybean hull and grape pomace. Biomass Convers Bior 2023, 13, 14939–14947. [Google Scholar] [CrossRef]
  70. Fatima, B.; Javed, M.M. Kinetics, thermodynamics, and physicochemical properties of 1, 4-α-d-glucan glucohydrolase from Aspergillus oryzae NRRL1560. Biomass Convers. Biorefinery 2021, 11, 3011–3022. [Google Scholar] [CrossRef]
  71. Mamo, J.; Kangwa, M.; Fernandez-Lahore, H.M.; Assefa, F. Optimization of media composition and growth conditions for production of milk-clotting protease (MCP) from Aspergillus oryzae DRDFS13 under solid-state fermentation. Braz. J. Microbiol. 2020, 51, 571–584. [Google Scholar] [CrossRef]
  72. Mahboob, S.; Ali, S. Pectin lyase productivity by a uv-irradiated Aspergillus oryzae mutant under carrot-koji process. J. Anim. Plant Sci.-JAPS 2022, 32, 1375–1384. [Google Scholar] [CrossRef]
  73. Qin, Y.; Qin, B.; Zhang, J.; Fu, Y.; Li, Q.; Luo, F.; Luo, Y.; He, H. Purification and enzymatic properties of a new thermostable endoglucanase from Aspergillus oryzae HML366. Int. Microbiol. 2023, 26, 579–589. [Google Scholar] [CrossRef] [PubMed]
  74. Ichikawa, K.; Shiono, Y.; Shintani, T.; Watanabe, A.; Kanzaki, H.; Gomi, K.; Koseki, T. Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter. J. Biosci. Bioeng. 2020, 129, 150–154. [Google Scholar] [CrossRef] [PubMed]
  75. Kotani, A.; Ozaki, T.; Takino, J.; Mochizuki, S.; Akimitsu, K.; Minami, A.; Oikawa, H. Heterologous expression of a polyketide synthase ACRTS2 in Aspergillus oryzae produces host-selective ACR toxins: Coproduction of minor metabolites. Biosci. Biotechnol. Biochem. 2021, 86, 287–293. [Google Scholar] [CrossRef] [PubMed]
  76. Elyasi Far, B.; Ahmadi, Y.; Yari Khosroshahi, A.; Dilmaghani, A. Microbial Alpha-Amylase Production: Progress, Challenges and Perspectives. Adv. Pharm. Bull. 2020, 10, 350–358. [Google Scholar] [CrossRef] [PubMed]
  77. Marengo, M.; Pezzilli, D.; Gianquinto, E.; Fissore, A.; Oliaro-Bosso, S.; Sgorbini, B.; Spyrakis, F.; Adinolfi, S. Evaluation of Porcine and Aspergillus oryzae α-Amylases as Possible Model for the Human Enzyme. Processes 2022, 10, 780. [Google Scholar] [CrossRef]
  78. Gomi, K. Regulatory mechanisms for amylolytic gene expression in the koji mold Aspergillus oryzae. Biosci. Biotechnol. Biochem. 2019, 83, 1385–1401. [Google Scholar] [CrossRef] [PubMed]
  79. Suzuki, K.; Tanaka, M.; Konno, Y.; Ichikawa, T.; Ichinose, S.; Hasegawa-Shiro, S.; Shintani, T.; Gomi, K. Distinct mechanism of activation of two transcription factors, AmyR and MalR, involved in amylolytic enzyme production in Aspergillus oryzae. Appl. Microbiol. Biotechnol. 2015, 99, 1805–1815. [Google Scholar] [CrossRef]
  80. Bakker, R.; Mani, M.; Carthew, R.W. The Wg and Dpp morphogens regulate gene expression by modulating the frequency of transcriptional bursts. eLife 2020, 9, e56076. [Google Scholar] [CrossRef]
  81. Takeshita, N. Coordinated process of polarized growth in filamentous fungi. Biosci. Biotechnol. Biochem. 2016, 80, 1693–1699. [Google Scholar] [CrossRef]
  82. Krijgsheld, P.; Bleichrodt, R.; van Veluw, G.J.; Wang, F.; Müller, W.H.; Dijksterhuis, J.; Wösten, H.A.B. Development in Aspergillus. Stud. Mycol. 2013, 74, 1–29. [Google Scholar] [CrossRef]
  83. Yasui, M.; Oda, K.; Masuo, S.; Hosoda, S.; Katayama, T.; Maruyama, J.-i.; Takaya, N.; Takeshita, N. Invasive growth of Aspergillus oryzae in rice koji and increase of nuclear number. Fungal Biol. Biotechnol. 2020, 7, 8. [Google Scholar] [CrossRef] [PubMed]
  84. Ichikawa, T.; Tanaka, M.; Watanabe, T.; Zhan, S.; Watanabe, A.; Shintani, T.; Gomi, K. Crucial role of the intracellular α-glucosidase MalT in the activation of the transcription factor AmyR essential for amylolytic gene expression in Aspergillus oryzae. Biosci. Biotechnol. Biochem. 2021, 85, 2076–2083. [Google Scholar] [CrossRef] [PubMed]
  85. Machida, M.; Asai, K.; Sano, M.; Tanaka, T.; Kumagai, T.; Terai, G.; Kusumoto, K.-I.; Arima, T.; Akita, O.; Kashiwagi, Y.; et al. Genome sequencing and analysis of Aspergillus oryzae. Nature 2005, 438, 1157–1161. [Google Scholar] [CrossRef]
  86. Higuchi, Y. Membrane Traffic in Aspergillus oryzae and Related Filamentous Fungi. J. Fungi 2021, 7, 534. [Google Scholar] [CrossRef]
  87. Chen, J.; Tonouchi, A. Copper ion (Cu2+) is involved in the transcription of the tyrosinase-encoding melB gene of Aspergillus oryzae in solid-state culture. Biosci. Biotechnol. Biochem. 2023, 88, 220–224. [Google Scholar] [CrossRef]
  88. Akao, T.; Yahara, A.; Sakamoto, K.; Yamada, O.; Akita, O.; Yoshida, T. Lack of endoplasmic reticulum 1,2-α-mannosidase activity that trims N-glycan Man9GlcNAc2 to Man8GlcNAc2 isomer B in a manE gene disruptant of Aspergillus oryzae. J. Biosci. Bioeng. 2012, 113, 438–441. [Google Scholar] [CrossRef] [PubMed]
  89. Koseki, T.; Ishida, N.; Hirota, R.; Shiono, Y.; Makabe, K. Mutational analysis of the effects of N-glycosylation sites on the activity and thermal stability of rutinosidase from Aspergillus oryzae. Enzym. Microb. Technol. 2022, 161, 110112. [Google Scholar] [CrossRef] [PubMed]
  90. Li, Q.; Higuchi, Y.; Tanabe, K.; Katakura, Y.; Takegawa, K. Secretory production of N-glycan-deleted glycoprotein in Aspergillus oryzae. J. Biosci. Bioeng. 2020, 129, 573–580. [Google Scholar] [CrossRef]
  91. Kimura, S.; Maruyama, J.-i.; Watanabe, T.; Ito, Y.; Arioka, M.; Kitamoto, K. In vivo imaging of endoplasmic reticulum and distribution of mutant α-amylase in Aspergillus oryzae. Fungal Genet. Biol. 2010, 47, 1044–1054. [Google Scholar] [CrossRef]
  92. Hayakawa, Y.; Ishikawa, E.; Shoji, J.-y.; Nakano, H.; Kitamoto, K. Septum-directed secretion in the filamentous fungus Aspergillus oryzae. Mol. Microbiol. 2011, 81, 40–55. [Google Scholar] [CrossRef]
  93. Srikanth, M.; Sandeep, T.S.R.S.; Sucharitha, K.; Godi, S. Biodegradation of plastic polymers by fungi: A brief review. Bioresour. Bioprocess. 2022, 9, 42. [Google Scholar] [CrossRef]
  94. Morilla, E.A.; Stegmann, P.M.; Tubio, G. Enzymatic cocktail production by a co-cultivation Solid-State Fermentation for detergent formulation. Food Bioprod. Process. 2023, 140, 110–121. [Google Scholar] [CrossRef]
  95. El-Wafai, N.A.; Farrag, A.M.I.; Abdel-Basit, H.M.; Hegazy, M.I.; Al-Goul, S.T.; Ashkan, M.F.; Al-Quwaie, D.A.; Alqahtani, F.S.; Amin, S.A.; Ismail, M.N.; et al. Eco-Friendly Degradation of Natural Rubber Powder Waste Using Some Microorganisms with Focus on Antioxidant and Antibacterial Activities of Biodegraded Rubber. Processes 2023, 11, 2350. [Google Scholar] [CrossRef]
  96. Varjani, S.; Upasani, V.N. Bioaugmentation of Pseudomonas aeruginosa NCIM 5514—A novel oily waste degrader for treatment of petroleum hydrocarbons. Bioresour. Technol. 2021, 319, 124240. [Google Scholar] [CrossRef] [PubMed]
  97. Chrysikou, L.P.; Dagonikou, V.; Dimitriadis, A.; Bezergianni, S. Waste cooking oils exploitation targeting EU 2020 diesel fuel production: Environmental and economic benefits. J. Clean. Prod. 2019, 219, 566–575. [Google Scholar] [CrossRef]
  98. Orjuela, A.; Clark, J. Green chemicals from used cooking oils: Trends, challenges, and opportunities. Curr. Opin. Green Sustain. Chem. 2020, 26, 100369. [Google Scholar] [CrossRef] [PubMed]
  99. Nasrabadi, A.E.; Ramavandi, B.; Bonyadi, Z. Recent progress in biodegradation of microplastics by Aspergillus sp. in aquatic environments. Colloid Interface Sci. Commun. 2023, 57, 100754. [Google Scholar] [CrossRef]
  100. Wang, Y.; Li, X.; Chen, X.; Siewers, V. CRISPR/Cas9-mediated point mutations improve α-amylase secretion in Saccharomyces cerevisiae. FEMS Yeast Res. 2022, 22, foac033. [Google Scholar] [CrossRef]
  101. Pham, T.A.; Tran, L.N.; Dam, T.H.; To, K.A. Valorization of Cassava Bagasse Using Co-culture of Aspergillus oryzae VS1 and Sporidiobolus pararoseus O1 in Solid-State Fermentation. Waste Biomass Valori 2022, 13, 3003–3012. [Google Scholar] [CrossRef]
  102. Song, L.; Chen, Y.; Du, Y.; Wang, X.; Guo, X.; Dong, J.; Xiao, D. Saccharomyces cerevisiae proteinase A excretion and wine making. World J. Microbiol. Biotechnol. 2017, 33, 210. [Google Scholar] [CrossRef]
  103. Sadh, P.K.; Duhan, S.; Duhan, J.S. Agro-industrial wastes and their utilization using solid state fermentation: A review. Bioresour. Bioprocess. 2018, 5, 1. [Google Scholar] [CrossRef]
  104. Shah, A.V.; Singh, A.; Sabyasachi Mohanty, S.; Kumar Srivastava, V.; Varjani, S. Organic solid waste: Biorefinery approach as a sustainable strategy in circular bioeconomy. Bioresour. Technol. 2022, 349, 126835. [Google Scholar] [CrossRef] [PubMed]
  105. Huang, H.; Niu, Y.; Jin, Q.; Qin, K.; Wang, L.; Shang, Y.; Zeng, B.; Hu, Z. Identification of Six Thiolases and Their Effects on Fatty Acid and Ergosterol Biosynthesis in Aspergillus oryzae. Appl. Environ. Microbiol. 2022, 88, e02372-21. [Google Scholar] [CrossRef]
  106. Uwineza, C.; Mahboubi, A.; Atmowidjojo, A.; Ramadhani, A.; Wainaina, S.; Millati, R.; Wikandari, R.; Niklasson, C.; Taherzadeh, M.J. Cultivation of edible filamentous fungus Aspergillus oryzae on volatile fatty acids derived from anaerobic digestion of food waste and cow manure. Bioresour. Technol. 2021, 337, 125410. [Google Scholar] [CrossRef] [PubMed]
  107. Nazir, M.T.; Soufiani, A.M.; Ferreira, J.A.; Sar, T.; Taherzadeh, M.J. Production of filamentous fungal biomass with increased oil content using olive oil as a carbon source. J. Chem. Technol. Biotechnol. 2022, 97, 2626–2635. [Google Scholar] [CrossRef]
  108. Iwamoto, N.; Sasaki, A.; Maizawa, T.; Hamada-Sato, N. Abalone Viscera Fermented with Aspergillus oryzae 001 Prevents Pressure Elevation by Inhibiting Angiotensin Converting Enzyme. Nutrients 2023, 15, 947. [Google Scholar] [CrossRef]
  109. Parchami, M.; Ferreira, J.A.; Taherzadeh, M.J. Brewing Process Development by Integration of Edible Filamentous Fungi to Upgrade the Quality of Brewer’s Spent Grain (BSG). Bioresources 2021, 16, 1686–1701. [Google Scholar] [CrossRef]
  110. Bangar, S.P.; Sandhu, K.S.; Purewal, S.S.; Kaur, M.; Kaur, P.; Siroha, A.K.; Kumari, K.; Singh, M.; Kumar, M. Fermented barley bran: An improvement in phenolic compounds and antioxidant properties. J. Food Process. Preserv. 2022, 46, e15543. [Google Scholar] [CrossRef]
  111. Ikram Ul, H.; Ashraf, S.; Nawaz, A.; Arshad, Y.; Mukhtar, H. Biosynthesis of β-galactosidase from Aspergillus oryzae using milk powder as substrate. Pak. J. Bot. 2021, 53, 273–279. [Google Scholar] [CrossRef]
  112. Kawa-Rygielska, J.; Pietrzak, W.; Lennartsson, P.R. High-Efficiency Conversion of Bread Residues to Ethanol and Edible Biomass Using Filamentous Fungi at High Solids Loading: A Biorefinery Approach. Appl. Sci. 2022, 12, 6405. [Google Scholar] [CrossRef]
  113. Ozturk, A.B.; Al-Shorgani, N.K.N.; Cheng, S.; Arasoglu, T.; Gulen, J.; Habaki, H.; Egashira, R.; Kalil, M.S.; Yusoff, W.M.W.; Cross, J.S. Two-step fermentation of cooked rice with Aspergillus oryzae and Clostridium acetobutylicum YM1 for biobutanol production. Biofuels 2022, 13, 579–585. [Google Scholar] [CrossRef]
  114. Guo, H.-N.; Wu, S.-B.; Tian, Y.-J.; Zhang, J.; Liu, H.-T. Application of machine learning methods for the prediction of organic solid waste treatment and recycling processes: A review. Bioresour. Technol. 2021, 319, 124114. [Google Scholar] [CrossRef]
  115. Sirohi, R.; Kumar Gaur, V.; Kumar Pandey, A.; Jun Sim, S.; Kumar, S. Harnessing fruit waste for poly-3-hydroxybutyrate production: A review. Bioresour. Technol. 2021, 326, 124734. [Google Scholar] [CrossRef] [PubMed]
  116. Chilakamarry, C.R.; Sakinah, A.M.M.; Zularisam, A.W.; Pandey, A. Glycerol waste to value added products and its potential applications. Syst. Microbiol. Biomanufacturing 2021, 1, 378–396. [Google Scholar] [CrossRef]
  117. Chaitanya Reddy, C.; Khilji, I.A.; Gupta, A.; Bhuyar, P.; Mahmood, S.; Saeed Al-Japairai, K.A.; Chua, G.K. Valorization of keratin waste biomass and its potential applications. J. Water Process Eng. 2021, 40, 101707. [Google Scholar] [CrossRef]
  118. Sharma, P.; Gaur, V.K.; Sirohi, R.; Varjani, S.; Hyoun Kim, S.; Wong, J.W.C. Sustainable processing of food waste for production of bio-based products for circular bioeconomy. Bioresour. Technol. 2021, 325, 124684. [Google Scholar] [CrossRef] [PubMed]
  119. Banat, I.M.; Carboué, Q.; Saucedo-Castañeda, G.; de Jesús Cázares-Marinero, J. Biosurfactants: The green generation of speciality chemicals and potential production using Solid-State fermentation (SSF) technology. Bioresour. Technol. 2021, 320, 124222. [Google Scholar] [CrossRef] [PubMed]
  120. Li, J.; Liu, B.; Feng, X.; Zhang, M.; Ding, T.; Zhao, Y.; Wang, C. Comparative proteome and volatile metabolome analysis of Aspergillus oryzae 3.042 and Aspergillus sojae 3.495 during koji fermentation. Food Res. Int. 2023, 165, 112527. [Google Scholar] [CrossRef]
  121. Robazza, A.; Welter, C.; Kubisch, C.; Baleeiro, F.C.; Ochsenreither, K.; Neumann, A. Co-Fermenting Pyrolysis Aqueous Condensate and Pyrolysis Syngas with Anaerobic Microbial Communities Enables L-Malate Production in a Secondary Fermentative Stage. Fermentation 2022, 8, 512. [Google Scholar] [CrossRef]
  122. Abid, K.; Jabri, J.; Yaich, H.; Malek, A.; Rekhis, J.; Kamoun, M. Nutritional value assessments of peanut hulls and valorization with exogenous fibrolytic enzymes extracted from a mixture culture of Aspergillus strains and Neurospora intermedia. Biomass Convers. Biorefinery 2022, 1–9. [Google Scholar] [CrossRef]
  123. Danner, C.; Mach, R.L.; Mach-Aigner, A.R. The phenomenon of strain degeneration in biotechnologically relevant fungi. Appl. Microbiol. Biotechnol. 2023, 107, 4745–4758. [Google Scholar] [CrossRef]
  124. Chi, Z.; Kong, C.-C.; Wang, Z.-Z.; Wang, Z.; Liu, G.-L.; Hu, Z.; Chi, Z.-M. The signaling pathways involved in metabolic regulation and stress responses of the yeast-like fungi Aureobasidium spp. Biotechnol. Adv. 2022, 55, 107898. [Google Scholar] [CrossRef] [PubMed]
  125. Sakekar, A.A.; Gaikwad, S.R.; Punekar, N.S. Protein expression and secretion by filamentous fungi. J. Biosci. 2021, 46, 5. [Google Scholar] [CrossRef]
  126. Li, Q.; Lu, J.; Liu, J.; Li, J.; Zhang, G.; Du, G.; Chen, J. High-throughput droplet microfluidics screening and genome sequencing analysis for improved amylase-producing Aspergillus oryzae. Biotechnol. Biofuels Bioprod. 2023, 16, 185. [Google Scholar] [CrossRef]
  127. Ntana, F.; Mortensen, U.H.; Sarazin, C.; Figge, R. Aspergillus: A Powerful Protein Production Platform. Catalysts 2020, 10, 1064. [Google Scholar] [CrossRef]
  128. Karaman, E.; Eyüpoğlu, A.E.; Mahmoudi Azar, L.; Uysal, S. Large-Scale Production of Anti-RNase A VHH Expressed in pyrG Auxotrophic Aspergillus oryzae. Curr. Issues Mol. Biol. 2023, 45, 4778–4795. [Google Scholar] [CrossRef]
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Figure 1. The cell factory based on A. oryzae and its applications.
Figure 1. The cell factory based on A. oryzae and its applications.
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Figure 2. Constitutional formula of KA (A); synthetic three-step chemo-enzymatic route (B). DFM (dimethyl formamide).
Figure 2. Constitutional formula of KA (A); synthetic three-step chemo-enzymatic route (B). DFM (dimethyl formamide).
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Figure 3. The biosynthetic route of KA production from glucose in A. oryzae. Adapted with permission from Refs. [38,40] 2024, Sumit Sharma et al.
Figure 3. The biosynthetic route of KA production from glucose in A. oryzae. Adapted with permission from Refs. [38,40] 2024, Sumit Sharma et al.
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Figure 4. The KA gene cluster in A. oryzae and its effect on KA production. Adapted with permission from Refs. [41,42,43,44,45] 2024, Sumit Sharma et al.
Figure 4. The KA gene cluster in A. oryzae and its effect on KA production. Adapted with permission from Refs. [41,42,43,44,45] 2024, Sumit Sharma et al.
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Figure 5. Protein secretion pathways in A. oryzae filaments. SV, secretory vesicle; CUPS, compartment for unconventional protein secretion.
Figure 5. Protein secretion pathways in A. oryzae filaments. SV, secretory vesicle; CUPS, compartment for unconventional protein secretion.
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Figure 6. Application prospects, and advantages and disadvantages of organic-rich waste treatment by cell factory.
Figure 6. Application prospects, and advantages and disadvantages of organic-rich waste treatment by cell factory.
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Figure 7. Microbial metabolism pathways involved in waste cooking oil degradation. Abbreviations: MIT (mitochondria), TCA cycle (tricarboxylic-acid cycle), LB (lipid body), DHAP (dihydroxyacetone phosphate), GA3P (glycerol-3-phosphate), PEP (phosphoenolpyruvic acid), OAA (oxaloacetic acid), PA (phosphatidic acid), LPA (lysophosphatidic acid), DAG (diacylglycerol), TAGs (triacylglycerols), FFA (free fatty acids), PYC (pyruvate carboxylase), ME (malic enzyme), ACL (ATP-citrate lyase), ACC (acyl-CoA carboxylase), FAS (fatty acid synthase), GUT1 (glycerol kinase), GPD1 (NAD+ dependent G3P dehydrogenase), GUT2 (FAD+ dependent G3P dehydrogenase), SCT1 (G3P acyltransferase), SLC1 (LPA acyltransferase), PAP (PA phosphohydrolase), DGA1 and DGA2 (DAG acyltransferases I and II), TGL4 (TAG intracellular lipase), TGL3 (a positive regulator of TGL4).
Figure 7. Microbial metabolism pathways involved in waste cooking oil degradation. Abbreviations: MIT (mitochondria), TCA cycle (tricarboxylic-acid cycle), LB (lipid body), DHAP (dihydroxyacetone phosphate), GA3P (glycerol-3-phosphate), PEP (phosphoenolpyruvic acid), OAA (oxaloacetic acid), PA (phosphatidic acid), LPA (lysophosphatidic acid), DAG (diacylglycerol), TAGs (triacylglycerols), FFA (free fatty acids), PYC (pyruvate carboxylase), ME (malic enzyme), ACL (ATP-citrate lyase), ACC (acyl-CoA carboxylase), FAS (fatty acid synthase), GUT1 (glycerol kinase), GPD1 (NAD+ dependent G3P dehydrogenase), GUT2 (FAD+ dependent G3P dehydrogenase), SCT1 (G3P acyltransferase), SLC1 (LPA acyltransferase), PAP (PA phosphohydrolase), DGA1 and DGA2 (DAG acyltransferases I and II), TGL4 (TAG intracellular lipase), TGL3 (a positive regulator of TGL4).
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Table 1. Secondary metabolites produced by A. oryzae.
Table 1. Secondary metabolites produced by A. oryzae.
MetaboliteGene SourceSubstrateStrainYieldReference
2,4′-dihydroxy-3′-methoxypropiophenoneCongenericSucroseRIB40-[27]
PyronesCongenericSolid rice medium- 1-[28]
N, N-dimethyldecylamine N-oxideCongenericPotato dextrose agarMK674278-[29]
Orsellinic acidHeterologousMaltoseNSAR1340.41 mg/Kg[30]
Non-ribosomal peptide pigmentsCongenericGlucoseBCC 7051265.09 ± 14.74 mg/L·d[24]
Flavonoid aglycones and cajaninstilbene acidCongenericCajanus cajan cell suspension culturesY-29-[31]
L-malic acidCongenericAcetateDSM 186312.08 ± 1.25 g/L[32]
L-malic acidCongenericGlucoseDSM 1863178 g/L[33]
L-malic acidCongenericGlucoseDSM 1863-[34]
L-malic acidCongenericGlucoseFMME-S-38164.9 g/L[35]
KACongenericGlucose-139.24 g/L[36]
GlucosamineCongenericPotato dextrose brothNCH-420.31 g/g[37]
1 The uncertain strain was screened from the environment by researchers.
Table 2. Several regulatory genes and their effects on KA yield.
Table 2. Several regulatory genes and their effects on KA yield.
StrainGene NameEncoded ProteinActing SiteGenetic ManipulationKA YieldReference
3.042kojRZn2+2Cys6 transcriptional activator-Overexpressed32.5 g/L[12]
RB40hirAHistone chaperonTranscription--[48]
3.042Aokap2Cell surface ferric reductaselaeA & kojAOverexpressedIncreased[49]
3.042Aokap5C2H2-type zinc-finger proteinkojT promotorOverexpressedIncreased[50]
3.042Aokap1Kojic acid related protein 1kojA, kojR and kojTDisruptedIncreased[51]
3.042AozfAZinc finger proteinTranscriptional activatorOverexpressedReduced[52]
RB40Aoatg8Enables phosphatidylethanolamine binding activity and protein tagAutophagyDisruptedIncreased[46]
RB40AoZip2IRT-like proteinResponse of metal ionsOverexpressedReduced[47]
Table 3. Producing industrial enzymes in A. oryzae.
Table 3. Producing industrial enzymes in A. oryzae.
StrainEnzymeSourcePositionAcetiveReference
MN894021XylanaseHomologousExtracellular0.37 U/mL[61]
ATCC 10124XylanaseHomologousExtracellular11.90 U/g DS 1[62]
SBS50PhytaseHomologousExtracellular506.12 U/g[63]
BM-DIAFructosyltransferaseHomologousExtracellular1.59 U/mL[64]
-α-amylaseHomologousExtracellular9868.12 U/gds[65]
NRRL695α-amylaseHomologousExtracellular14.076 U/mL[66]
S719β-fructofuranosidaseHomologousExtracellular155.4 U/mL[67]
S719FructosyltransferaseHomologousExtracellular12 U/mL[68]
NRRL695TannaseHomologousIntracellular-[69]
NRRL15601,4-α-D-glucan glucohydrolaseHomologousExtracellular-[70]
DRDFS13Milk-clotting proteaseHomologousExtracellular137.58 U/mL[71]
ISL-9Pectin lyaseHomologousExtracellular9.26 U/mL[72]
HML366EndoglucanaseHomologousExtracellular-[73]
AOK11Recombinant tannaseHeterogenousExtracellular-[74]
NSPlD1Polyketide synthaseHeterogenousIntracellular-[75]
1 DS, dried solids.
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MDPI and ACS Style

Sun, Z.; Wu, Y.; Long, S.; Feng, S.; Jia, X.; Hu, Y.; Ma, M.; Liu, J.; Zeng, B. Aspergillus oryzae as a Cell Factory: Research and Applications in Industrial Production. J. Fungi 2024, 10, 248. https://doi.org/10.3390/jof10040248

AMA Style

Sun Z, Wu Y, Long S, Feng S, Jia X, Hu Y, Ma M, Liu J, Zeng B. Aspergillus oryzae as a Cell Factory: Research and Applications in Industrial Production. Journal of Fungi. 2024; 10(4):248. https://doi.org/10.3390/jof10040248

Chicago/Turabian Style

Sun, Zeao, Yijian Wu, Shihua Long, Sai Feng, Xiao Jia, Yan Hu, Maomao Ma, Jingxin Liu, and Bin Zeng. 2024. "Aspergillus oryzae as a Cell Factory: Research and Applications in Industrial Production" Journal of Fungi 10, no. 4: 248. https://doi.org/10.3390/jof10040248

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