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14 pages, 4412 KiB

Open AccessArticle

Understanding the Essential Metabolic Nodes in the Synthesis of 4-Acetylantroquinol B (4-AAQB) by Antrodia cinnamomea Using Transcriptomic Analysis

by Yuhan Jin, Huan Liu, Yuchen Ning, Yew-Min Tzeng, Li Deng and Fang Wang

Fermentation 2023, 9(6), 542; https://doi.org/10.3390/fermentation9060542 - 05 Jun 2023

Viewed by 857

Abstract

4-Acetylantroquinol B (4-AAQB) is a ubiquinone that has been shown to have multiple anticancer activities and is only found in the rare medicinal fungus A. cinnamomea in Taiwan. The large-scale production and application of 4-AAQB is thus limited due to the high host [...] Read more.

4-Acetylantroquinol B (4-AAQB) is a ubiquinone that has been shown to have multiple anticancer activities and is only found in the rare medicinal fungus A. cinnamomea in Taiwan. The large-scale production and application of 4-AAQB is thus limited due to the high host specificity, long production cycle, and low 4-AAQB content of A. cinnamomea. Additionally, the lack of molecular genetic studies on A. cinnamomea has hindered the study of the synthetic pathway of 4-AAQB. In this work, transcriptomic analysis was conducted to understand the essential metabolic nodes in the synthesis of 4-AAQB by A. cinnamomea based on the differences using glucose and fructose as carbon sources, respectively. The results showed that the glyoxylate and TCA cycle, terpenoid synthesis pathway, and the quinone ring modification pathway were clarified as the most significant factors associated with 4-AAQB synthesis. The enzymes ACS, ACU7, ACUE, GPS, PPT, P450, GEDA, YAT1, CAT2, and METXA in these pathways were the essential metabolic nodes in the synthesis of 4-AAQB. When fructose was used as the substrate, the expressions of these enzymes were upregulated, and the synthesis of some important intermediate metabolites was enhanced, thus promoting the accumulation of 4-AAQB. Our work understood the mechanism of fructose promoting the synthesis of 4-AAQB and identified the essential metabolic nodes which could provide the theoretical basis for the development of fermentation strategies to produce 4-AAQB by A. cinnamomea. Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

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12 pages, 2559 KiB

Open AccessArticle

Dichlororesorcinols Produced by a Rhizospheric Fungi of Panax notoginseng as Potential ERK2 Inhibitors

by Yingying Wu, Mengyue Zhang, Jinyan Xue, Juan Cheng, Mingyu Xia, Xunyong Zhou and Yixuan Zhang

Fermentation 2023, 9(6), 517; https://doi.org/10.3390/fermentation9060517 - 27 May 2023

Viewed by 849

Abstract

Rhizospheric fungi of medicinal plants are important sources for discovering novel and valuable secondary metabolites with potential pharmaceutical applications. In our research, five new dichlororesorcinols (1–5) and five known metabolites (6–10) were separated from the secondary metabolites of Chaetomium [...] Read more.

Rhizospheric fungi of medicinal plants are important sources for discovering novel and valuable secondary metabolites with potential pharmaceutical applications. In our research, five new dichlororesorcinols (1–5) and five known metabolites (6–10) were separated from the secondary metabolites of Chaetomium sp. SYP-F6997, which was isolated from the rhizospheric soil of Panax notoginseng. The identification of these compounds was confirmed using various spectroscopic techniques including ESI-MS, UV, IR, NMR and ECD analyses. These findings highlight the potential of rhizospheric fungi as a rich source of novel bioactive compounds. In addition, chiral HPLC was used to successfully separate the enantiomers compound 4 and compound 5, and TDDFT-ECD/optical rotation calculations were used to test their absolute configurations. This is the first report of compounds 1–10 from the genus Chaetomium, and the first report of compounds 1–5 and 7 from the family Chaetomiaceae. We proposed plausible biosynthetic pathways for dichlororesorcinols 1–6 based on their analogous carbon skeleton. These findings provide insights into the biosynthesis of these compounds and expand our understanding of the secondary metabolites produced by Chaetomium sp. SYP-F6997. To evaluate their potential as therapeutic agents, we investigated the cytotoxic activity of all the isolated metabolites against cell lines H9, HL-60, K562, THP-1 and CEM using the MTT method. The new compounds 1 and 2 exhibited significant cytotoxic activities against H9 and CEM, with IC50 values lower than 10 µM. To further explore the potential mechanisms of action, we performed molecular docking studies to investigate the interactions between compounds 1 and 2 with the potential target ERK2. Our results demonstrate that the compounds exhibited strong binding abilities and formed H-bond interactions with ERK2, providing support for their potent antitumor activities and promising potential as lead molecules for the development of antitumor therapeutics. Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

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23 pages, 39243 KiB

Open AccessArticle

A Study of the Metabolic Profiles of Penicillium dimorphosporum KMM 4689 Which Led to Its Re-Identification as Penicillium hispanicum

by Liliana E. Nesterenko, Roman S. Popov, Olesya I. Zhuravleva, Natalya N. Kirichuk, Viktoria E. Chausova, Kirill S. Krasnov, Mikhail V. Pivkin, Ekaterina A. Yurchenko, Marina P. Isaeva and Anton N. Yurchenko

Fermentation 2023, 9(4), 337; https://doi.org/10.3390/fermentation9040337 - 28 Mar 2023

Cited by 2 | Viewed by 1400

Abstract

Changes in cultivation conditions, in particular salinity and temperature, affect the production of secondary fungal metabolites. In this work, the extracts of fungus previously described as Penicillium dimorphosporum cultivated in various salinity and temperature conditions were investigated using HPLC UV/MS techniques, and their [...] Read more.

Changes in cultivation conditions, in particular salinity and temperature, affect the production of secondary fungal metabolites. In this work, the extracts of fungus previously described as Penicillium dimorphosporum cultivated in various salinity and temperature conditions were investigated using HPLC UV/MS techniques, and their DPPH radical scavenging and cytotoxicity activities against human prostate cancer PC-3 cells and rat cardiomyocytes H9c2 were tested. In total, 25 compounds, including 13 desoxyisoaustamide-related alkaloids and eight anthraquinones, were identified in the studied extracts and their relative amounts were estimated. The production of known neuroprotective alkaloids 5, 6 and other brevianamide alkaloids was increased in hypersaline and high-temperature conditions, and this may be an adaptation to extreme conditions. On the other hand, hyposalinity stress may induce the synthesis of unidentified antioxidants with low cytotoxicity that could be very interesting for future investigation. The study of secondary metabolites of the strain KMM 4689 showed that although brevianamide-related alkaloids and anthraquinone pigments are widely distributed in various fungi, these metabolites have not been described for P. dimorphosporum and related species. For this reason, the strain KMM 4689 was re-sequenced using the β-tubulin gene and ITS regions as molecular markers and further identified as P. hispanicum. Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

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14 pages, 2289 KiB

Open AccessArticle

Effect and Mechanism of Lepista nuda Mycelia Obtained via In Vitro Culture on the Lifespan of Drosophila melanogaster

by Jinzhe Li, Yaqin Huang, Dezhi Wang, Nailiang Zhu and Xinrong Qiao

Fermentation 2023, 9(3), 212; https://doi.org/10.3390/fermentation9030212 - 23 Feb 2023

Viewed by 1237

Abstract

To provide a theoretical basis for biogenic fly-killing pesticides, in this study, we sought to examine the lethal effects of Lepista nuda mycelium-supplemented diets in Drosophila melanogaster. In doing so, we also studied the effects of Lepista nuda mycelium-supplemented diets on lifespan, [...] Read more.

To provide a theoretical basis for biogenic fly-killing pesticides, in this study, we sought to examine the lethal effects of Lepista nuda mycelium-supplemented diets in Drosophila melanogaster. In doing so, we also studied the effects of Lepista nuda mycelium-supplemented diets on lifespan, antioxidant enzyme activity, peroxide content, relative transcript amounts of antioxidant enzyme genes, signaling pathways, and lifespan. Lower Lepista nuda mycelium-supplemented diets activated the antioxidant system and prolonged lifespan, while higher mycelium-supplemented diets had a significant toxic effect. After the administration of mycelium-supplemented diets for 24 h, the highest corrected mortality (41.96%) and lifespan inhibition rates (96.50%) were observed. In addition, the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); the relative transcript amounts of the key antioxidant enzyme genes SOD, CAT, and TrxR-1; and the lifespan genes Hep and Nrf2 were found to be the lowest, while the contents of the oxidation products malondialdehyde (MDA), protein carbonylation product (PCO), and triglyceride (TG); the relative transcript amounts of the signaling pathway-related genes S6K, TOR, and Keap-1; and the lifespan gene MTH were observed to be the highest after 48 h. Higher Lepista nuda mycelium-supplemented diets significantly inhibited lifespan, acting via the initiation of oxidative stress systems. Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

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10 pages, 2042 KiB

Open AccessArticle

Improved Production of α-Amylase by Aspergillus terreus in Presence of Oxygen-Vector

by Alexandra Cristina Blaga, Dan Caşcaval and Anca Irina Galaction

Fermentation 2022, 8(6), 271; https://doi.org/10.3390/fermentation8060271 - 10 Jun 2022

Cited by 3 | Viewed by 1780

Abstract

n-Dodecane has been investigated as an oxygen-vector for improving α-amylase biosynthesis using the strain Aspergillus terreus. In aerobic microbial cultivation, continuous supply of oxygen is required especially due to its low solubility in the growth medium, in particular at high viscosity, [...] Read more.

n-Dodecane has been investigated as an oxygen-vector for improving α-amylase biosynthesis using the strain Aspergillus terreus. In aerobic microbial cultivation, continuous supply of oxygen is required especially due to its low solubility in the growth medium, in particular at high viscosity, but the limitations of oxygen mass transfer in these systems can be overcome by the addition of water-insoluble compounds which possess a strong affinity for oxygen, namely oxygen-vectors. The use of n-dodecane (as an oxygen-vector) in the fermentation medium of A. terreus can significantly improve the bioprocess performance and enhance α-amylase production. Using 5% n-dodecane at 35 °C, an increase of 1.8–2 times in the enzymatic activity was recorded. In the oxygen-vector’s absence, the highest amount of biomass was obtained at 35 °C, while in the presence of 5% vol. n-dodecane, the amount of fungal biomass increased by approximately 70%, with a shift in optimum temperature to 40 °C, generating also an enzymatic activity increase of 2.30 times. Moreover, the oxygen-vector’s addition in the fermentation broth influenced the fungal morphological development in the form of larger pellets with a more compact structure compared to the system without n-dodecane, with a positive effect on the fermentation performance (higher α-amylase activity production). Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

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Review

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43 pages, 6306 KiB

Open AccessReview

Aspergillus nidulans—Natural Metabolites Powerhouse: Structures, Biosynthesis, Bioactivities, and Biotechnological Potential

by Kholoud F. Ghazawi, Sarah A. Fatani, Shaimaa G. A. Mohamed, Gamal A. Mohamed and Sabrin R. M. Ibrahim

Fermentation 2023, 9(4), 325; https://doi.org/10.3390/fermentation9040325 - 25 Mar 2023

Cited by 4 | Viewed by 1431

Abstract

Nowadays, finding out new natural scaffolds of microbial origin increases at a higher rate than in the past decades and represents an auspicious route for reinvigorating the pool of compounds entering pharmaceutical industries. Fungi serve as a depository of fascinating, structurally unique metabolites [...] Read more.

Nowadays, finding out new natural scaffolds of microbial origin increases at a higher rate than in the past decades and represents an auspicious route for reinvigorating the pool of compounds entering pharmaceutical industries. Fungi serve as a depository of fascinating, structurally unique metabolites with considerable therapeutic significance. Aspergillus genus represents one of the most prolific genera of filamentous fungi. Aspergillus nidulans Winter G. is a well-known and plentiful source of bioactive metabolites with abundant structural diversity, including terpenoids, benzophenones, sterols, alkaloids, xanthones, and polyketides, many of which display various bioactivities, such as cytotoxicity, antioxidant, anti-inflammatory, antiviral, and antimicrobial activities. The current work is targeted to survey the reported literature on A. nidulans, particularly its metabolites, biosynthesis, and bioactivities, in addition to recent reports on its biotechnological potential. From 1953 till November 2022, relying on the stated data, 206 metabolites were listed, with more than 100 references. Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

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17 pages, 373 KiB

Open AccessReview

Yeast Carotenoids: Cost-Effective Fermentation Strategies for Health Care Applications

by Debarati Paul, Panda Kusuma Kumari and Nahid Siddiqui

Fermentation 2023, 9(2), 147; https://doi.org/10.3390/fermentation9020147 - 02 Feb 2023

Cited by 15 | Viewed by 3450

Abstract

Carotenoid production from oleaginous red yeast has been considered as a safe alternative to chemically synthesized carotenoids commonly used in the food industry, since plant-based carotenoids are expensive and an irregular source for obtaining pigments. This is a summative review on the factors [...] Read more.

Carotenoid production from oleaginous red yeast has been considered as a safe alternative to chemically synthesized carotenoids commonly used in the food industry, since plant-based carotenoids are expensive and an irregular source for obtaining pigments. This is a summative review on the factors affecting carotenoid production, cost-effective production strategies using various inexpensive feedstock, metabolic engineering, and strain improvisation. The review specially highlights the various potential applications of carotenoids as anti-microbial, anti-viral, antioxidant, anti-cancerous, anti-malarial agents, etc. The importance of such natural and easily available resources for prevention, evasion, or cure of emerging diseases and their plausible nutraceutical effect demands exhaustive research in this area. Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

21 pages, 3396 KiB

Open AccessReview

The Genus Chrysosporium: A Potential Producer of Natural Products

by Yifei Wang, Xiaowen Yang, Yanjing Li, Bo Wang and Ting Shi

Fermentation 2023, 9(1), 76; https://doi.org/10.3390/fermentation9010076 - 16 Jan 2023

Cited by 1 | Viewed by 1863

Abstract

Chrysosporium, a genus of ascomycete fungi in the family Onygenaceae, has the ability to produce abundant new bioactive natural products, providing a structural foundation in drug development. This review includes the sources, distribution, biological activities and structural characteristics of the compounds [...] Read more.

Chrysosporium, a genus of ascomycete fungi in the family Onygenaceae, has the ability to produce abundant new bioactive natural products, providing a structural foundation in drug development. This review includes the sources, distribution, biological activities and structural characteristics of the compounds isolated from Chrysosporium from 1984 to 2021. The results show that 66% of the compounds isolated from Chrysosporium are new natural products. More than half of the Chrysosporium-isolated compounds are from marine-derived Chrysosporium. The chemical structures of Chrysosporium-derived compounds have different skeletons, which are concentrated in alkaloids, polyketides, and lactones. Eighty percent of the natural products isolated from Chrysosporium have been found to have various biological activities, including cytotoxic, antibacterial, antifungal and enzyme-inhibitory activities. These results demonstrate the potential of Chrysosporium for producing new bioactive secondary metabolites, which can be used as the structural basis for developing new drugs. Full article

(This article belongs to the Special Issue New Research on Fungal Secondary Metabolites)

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