Editorial

3 pages, 172 KiB

Open AccessEditorial

by Eung-Soo Kim

Biomolecules 2021, 11(2), 134; https://doi.org/10.3390/biom11020134 - 21 Jan 2021

Cited by 5 | Viewed by 3029

The discovery and development of actinomycete secondary metabolites (ASMs) have played pivotal roles in the fields of human medicine and its related biotechnology sectors over the past several decades [...] Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

Research

Jump to: Editorial, Review

19 pages, 3628 KiB

Open AccessArticle

Actinomycetes Enrich Soil Rhizosphere and Improve Seed Quality as well as Productivity of Legumes by Boosting Nitrogen Availability and Metabolism

by Hamada AbdElgawad, Walid Abuelsoud, Mahmoud M. Y. Madany, Samy Selim, Gaurav Zinta, Ahmed S. M. Mousa and Wael N. Hozzein

Biomolecules 2020, 10(12), 1675; https://doi.org/10.3390/biom10121675 - 15 Dec 2020

Cited by 57 | Viewed by 7406

Abstract

The use of actinomycetes for improving soil fertility and plant production is an attractive strategy for developing sustainable agricultural systems due to their effectiveness, eco-friendliness, and low production cost. Out of 17 species isolated from the soil rhizosphere of legume crops, 4 bioactive [...] Read more.

The use of actinomycetes for improving soil fertility and plant production is an attractive strategy for developing sustainable agricultural systems due to their effectiveness, eco-friendliness, and low production cost. Out of 17 species isolated from the soil rhizosphere of legume crops, 4 bioactive isolates were selected and their impact on 5 legumes: soybean, kidney bean, chickpea, lentil, and pea were evaluated. According to the morphological and molecular identification, these isolates belong to the genus Streptomyces. Here, we showed that these isolates increased soil nutrients and organic matter content and improved soil microbial populations. At the plant level, soil enrichment with actinomycetes increased photosynthetic reactions and eventually increased legume yield. Actinomycetes also increased nitrogen availability in soil and legume tissue and seeds, which induced the activity of key nitrogen metabolizing enzymes, e.g., glutamine synthetase, glutamate synthase, and nitrate reductase. In addition to increased nitrogen-containing amino acids levels, we also report high sugar, organic acids, and fatty acids as well as antioxidant phenolics, mineral, and vitamins levels in actinomycete treated legume seeds, which in turn improved their seed quality. Overall, this study shed the light on the impact of actinomycetes on enhancing the quality and productivity of legume crops by boosting the bioactive primary and secondary metabolites. Moreover, our findings emphasize the positive role of actinomycetes in improving the soil by enriching its microbial population. Therefore, our data reinforce the usage of actinomycetes as biofertilizers to provide sustainable food production and achieve biosafety. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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14 pages, 1103 KiB

Open AccessArticle

8-Deoxy-Rifamycin Derivatives from Amycolatopsis mediterranei S699 ΔrifT Strain

by Feng Ye, Yanrong Shi, Shengliang Zhao, Zhiying Li, Haoxin Wang, Chunhua Lu and Yuemao Shen

Biomolecules 2020, 10(9), 1265; https://doi.org/10.3390/biom10091265 - 02 Sep 2020

Cited by 12 | Viewed by 2533

Abstract

Proansamycin X, a hypothetical earliest macrocyclic precursor in the biosynthesis of rifamycin, had never been isolated and identified. According to bioinformatics analysis, it was proposed that RifT (a putative NADH-dependent dehydrogenase) may be a candidate target responsible for the dehydrogenation of proansamycin X. [...] Read more.

Proansamycin X, a hypothetical earliest macrocyclic precursor in the biosynthesis of rifamycin, had never been isolated and identified. According to bioinformatics analysis, it was proposed that RifT (a putative NADH-dependent dehydrogenase) may be a candidate target responsible for the dehydrogenation of proansamycin X. In this study, the mutant strain Amycolatopsis mediterranei S699 ΔrifT was constructed by deleting the rifT gene. From this strain, eleven 8-deoxy-rifamycin derivatives (1–11) and seven known analogues (12–18) were isolated. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Compound 1 is a novel amide N-glycoside of seco-rifamycin. Compounds 2 and 3 feature conserved 11,12-seco-rifamycin W skeleton. The diverse post-modifications in the polyketide chain led to the production of 4–11. Compounds 2, 3, 5, 6, 13 and 15 exhibited antibacterial activity against Staphylococcus aureus (MIC (minimal inhibitory concentration) values of 10, 20, 20, 20, 40 and 20 μg/mL, respectively). Compounds 14, 15, 16, 17 and 18 showed potent antiproliferative activity against KG1 cells with IC₅₀ (half maximal inhibitory concentration) values of 14.91, 44.78, 2.16, 18.67 and 8.07 μM, respectively. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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19 pages, 4644 KiB

Open AccessArticle

Functional Analysis of P450 Monooxygenase SrrO in the Biosynthesis of Butenolide-Type Signaling Molecules in Streptomyces rochei

by Aiko Teshima, Nozomi Hadae, Naoto Tsuda and Kenji Arakawa

Biomolecules 2020, 10(9), 1237; https://doi.org/10.3390/biom10091237 - 25 Aug 2020

Cited by 7 | Viewed by 2568

Abstract

Streptomyces rochei 7434AN4 produces two structurally unrelated polyketide antibiotics lankacidin and lankamycin, and their biosynthesis is tightly controlled by butenolide-type signaling molecules SRB1 and SRB2. SRBs are synthesized by SRB synthase SrrX, and induce lankacidin and lankamycin production at 40 nM concentration. We [...] Read more.

Streptomyces rochei 7434AN4 produces two structurally unrelated polyketide antibiotics lankacidin and lankamycin, and their biosynthesis is tightly controlled by butenolide-type signaling molecules SRB1 and SRB2. SRBs are synthesized by SRB synthase SrrX, and induce lankacidin and lankamycin production at 40 nM concentration. We here investigated the role of a P450 monooxygenase gene srrO (orf84), which is located adjacent to srrX (orf85), in SRB biosynthesis. An srrO mutant KA54 accumulated lankacidin and lankamycin at a normal level when compared with the parent strain. To elucidate the chemical structures of the signaling molecules accumulated in KA54 (termed as KA54-SRBs), this mutant was cultured (30 L) and the active components were purified. Two active components (KA54-SRB1 and KA54-SRB2) were detected in ESI-MS and chiral HPLC analysis. The molecular formulae for KA54-SRB1 and KA54-SRB2 are C₁₅H₂₆O₄ and C₁₆H₂₈O₄, whose values are one oxygen smaller and two hydrogen larger when compared with those for SRB1 and SRB2, respectively. Based on extensive NMR analysis, the signaling molecules in KA54 were determined to be 6′-deoxo-SRB1 and 6′-deoxo-SRB2. Gel shift analysis indicated that a ligand affinity of 6′-deoxo-SRB1 to the specific receptor SrrA was 100-fold less than that of SRB1. We performed bioconversion of the synthetic 6′-deoxo-SRB1 in the Streptomyces lividans recombinant carrying SrrO-expression plasmid. Substrate 6′-deoxo-SRB1 was converted through 6′-deoxo-6′-hydroxy-SRB1 to SRB1 in a time-dependent manner. Thus, these results clearly indicated that SrrO catalyzes the C-6′ oxidation at a final step in SRB biosynthesis. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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11 pages, 890 KiB

Open AccessArticle

Naphthoquinone-Based Meroterpenoids from Marine-Derived Streptomyces sp. B9173

by Xinqian Shen, Xiaozheng Wang, Tingting Huang, Zixin Deng and Shuangjun Lin

Biomolecules 2020, 10(8), 1187; https://doi.org/10.3390/biom10081187 - 15 Aug 2020

Cited by 15 | Viewed by 3259

Abstract

Naphthoquinone-based meroterpenoids are hybrid polyketide-terpenoid natural products with chemical diversity and a broad range of biological activities. Here, we report the isolation of a group of naphthoquinone-containing compounds from Streptomyces sp. B9173, and their structures were elucidated by using a combination of spectroscopic [...] Read more.

Naphthoquinone-based meroterpenoids are hybrid polyketide-terpenoid natural products with chemical diversity and a broad range of biological activities. Here, we report the isolation of a group of naphthoquinone-containing compounds from Streptomyces sp. B9173, and their structures were elucidated by using a combination of spectroscopic techniques, including 1D, 2D NMR, and high-resolution mass (HRMS) analysis. Seven flaviogeranin congeners or intermediates, three of which were new, have been derived from common naphthoquinone backbone and subsequent oxidation, methylation, prenylation, and amino group incorporation. Both flaviogeranin B1 (1) and B (2) contain an amino group which was incorporated into the C8 of 1,3,6,8-terhydroxynaphthalene (THN). Flaviogeranin D (3) contains an intact C-geranylgeranyl residue attached to the C2 of THN, while the O-geranylgeranyl group of 2 links with the hydroxyl on the C2 site of THN. Four compounds were selected and tested for antibacterial activity and cytotoxicity, with 3 and flaviogeranin C2 (5) displaying potent activity against selected bacteria and cancer cell lines. In light of the structure features of isolated compounds and the biosynthetic genes, a biosynthetic pathway of naphthoquinone-based flaviogeranins has been proposed. These isolated compounds not only extend the structural diversity but also represent new insights into the biosynthesis of naphthoquinone-based meroterpenoids. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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11 pages, 1063 KiB

Open AccessArticle

Development of 6′-N-Acylated Isepamicin Analogs with Improved Antibacterial Activity against Isepamicin-Resistant Pathogens

by Yeon Hee Ban, Myoung Chong Song, Hee Jin Kim, Heejeong Lee, Jae Bok Wi, Je Won Park, Dong Gun Lee and Yeo Joon Yoon

Biomolecules 2020, 10(6), 893; https://doi.org/10.3390/biom10060893 - 11 Jun 2020

Cited by 4 | Viewed by 2594

Abstract

The development of new aminoglycoside (AG) antibiotics has been required to overcome the resistance mechanism of AG-modifying enzymes (AMEs) of AG-resistant pathogens. The AG acetyltransferase, AAC(6′)-APH(2″), one of the most typical AMEs, exhibiting substrate promiscuity towards a variety of AGs and acyl-CoAs, was [...] Read more.

The development of new aminoglycoside (AG) antibiotics has been required to overcome the resistance mechanism of AG-modifying enzymes (AMEs) of AG-resistant pathogens. The AG acetyltransferase, AAC(6′)-APH(2″), one of the most typical AMEs, exhibiting substrate promiscuity towards a variety of AGs and acyl-CoAs, was employed to enzymatically synthesize new 6′-N-acylated isepamicin (ISP) analogs, 6′-N-acetyl/-propionyl/-malonyl ISPs. They were all active against the ISP-resistant Gram-negative bacteria tested, and the 6′-N-acetyl ISP displayed reduced toxicity compared to ISP in vitro. This study demonstrated the importance of the modification of the 6′-amino group in circumventing AG-resistance and the potential of regioselective enzymatic modification of AG scaffolds for the development of more robust AG antibiotics. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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18 pages, 4161 KiB

Open AccessArticle

Comparative Genomics Determines Strain-Dependent Secondary Metabolite Production in Streptomyces venezuelae Strains

by Woori Kim, Namil Lee, Soonkyu Hwang, Yongjae Lee, Jihun Kim, Suhyung Cho, Bernhard Palsson and Byung-Kwan Cho

Biomolecules 2020, 10(6), 864; https://doi.org/10.3390/biom10060864 - 05 Jun 2020

Cited by 10 | Viewed by 4523

Abstract

Streptomyces venezuelae is well known to produce various secondary metabolites, including chloramphenicol, jadomycin, and pikromycin. Although many strains have been classified as S. venezuelae species, only a limited number of strains have been explored extensively for their genomic contents. Moreover, genomic differences and [...] Read more.

Streptomyces venezuelae is well known to produce various secondary metabolites, including chloramphenicol, jadomycin, and pikromycin. Although many strains have been classified as S. venezuelae species, only a limited number of strains have been explored extensively for their genomic contents. Moreover, genomic differences and diversity in secondary metabolite production between the strains have never been compared. Here, we report complete genome sequences of three S. venezuelae strains (ATCC 10712, ATCC 10595, and ATCC 21113) harboring chloramphenicol and jadomycin biosynthetic gene clusters (BGC). With these high-quality genome sequences, we revealed that the three strains share more than 85% of total genes and most of the secondary metabolite biosynthetic gene clusters (smBGC). Despite such conservation, the strains produced different amounts of chloramphenicol and jadomycin, indicating differential regulation of secondary metabolite production at the strain level. Interestingly, antagonistic production of chloramphenicol and jadomycin was observed in these strains. Through comparison of the chloramphenicol and jadomycin BGCs among the three strains, we found sequence variations in many genes, the non-coding RNA coding regions, and binding sites of regulators, which affect the production of the secondary metabolites. We anticipate that these genome sequences of closely related strains would serve as useful resources for understanding the complex secondary metabolism and for designing an optimal production process using Streptomyces strains. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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15 pages, 2265 KiB

Open AccessArticle

Subtilisin-Involved Morphology Engineering for Improved Antibiotic Production in Actinomycetes

by Yuanting Wu, Qianjin Kang, Li-Li Zhang and Linquan Bai

Biomolecules 2020, 10(6), 851; https://doi.org/10.3390/biom10060851 - 03 Jun 2020

Cited by 11 | Viewed by 3094

Abstract

In the submerged cultivation of filamentous microbes, including actinomycetes, complex morphology is one of the critical process features for the production of secondary metabolites. Ansamitocin P-3 (AP-3), an antitumor agent, is a secondary metabolite produced by Actinosynnema pretiosum ATCC 31280. An excessive mycelial [...] Read more.

In the submerged cultivation of filamentous microbes, including actinomycetes, complex morphology is one of the critical process features for the production of secondary metabolites. Ansamitocin P-3 (AP-3), an antitumor agent, is a secondary metabolite produced by Actinosynnema pretiosum ATCC 31280. An excessive mycelial fragmentation of A. pretiosum ATCC 31280 was observed during the early stage of fermentation. Through comparative transcriptomic analysis, a subtilisin-like serine peptidase encoded gene APASM_4178 was identified to be responsible for the mycelial fragmentation. Mutant WYT-5 with the APASM_4178 deletion showed increased biomass and improved AP-3 yield by 43.65%. We also found that the expression of APASM_4178 is specifically regulated by an AdpA-like protein APASM_1021. Moreover, the mycelial fragmentation was alternatively alleviated by the overexpression of subtilisin inhibitor encoded genes, which also led to a 46.50 ± 0.79% yield increase of AP-3. Furthermore, APASM_4178 was overexpressed in salinomycin-producing Streptomyces albus BK 3-25 and validamycin-producing S. hygroscopicus TL01, which resulted in not only dispersed mycelia in both strains, but also a 33.80% yield improvement of salinomycin to 24.07 g/L and a 14.94% yield improvement of validamycin to 21.46 g/L. In conclusion, our work elucidates the involvement of a novel subtilisin-like serine peptidase in morphological differentiation, and modulation of its expression could be an effective strategy for morphology engineering and antibiotic yield improvement in actinomycetes. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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14 pages, 3217 KiB

Open AccessArticle

Understand the Specific Regio- and Enantioselectivity of Fluostatin Conjugation in the Post-Biosynthesis

by Yuanqi Wang, Changsheng Zhang, Yi-Lei Zhao, Rosalinda Zhao and Kendall N. Houk

Biomolecules 2020, 10(6), 815; https://doi.org/10.3390/biom10060815 - 26 May 2020

Cited by 14 | Viewed by 3581

Abstract

Fluostatins, benzofluorene-containing aromatic polyketides in the atypical angucycline family, conjugate into dimeric and even trimeric compounds in the post-biosynthesis. The formation of the C–C bond involves a non-enzymatic stereospecific coupling reaction. In this work, the unusual regio- and enantioselectivities were rationalized by density [...] Read more.

Fluostatins, benzofluorene-containing aromatic polyketides in the atypical angucycline family, conjugate into dimeric and even trimeric compounds in the post-biosynthesis. The formation of the C–C bond involves a non-enzymatic stereospecific coupling reaction. In this work, the unusual regio- and enantioselectivities were rationalized by density functional theory calculations with the M06-2X (SMD, water)/6–311 + G(d,p)//6–31G(d) method. These DFT calculations reproduce the lowest energy C1-(R)-C10′-(S) coupling pathway observed in a nonenzymatic reaction. Bonding of the reactive carbon atoms (C1 and C10′) of the two reactant molecules maximizes the HOMO–LUMO interactions and Fukui function involving the highest occupied molecular orbital (HOMO) of nucleophile p-QM and lowest unoccupied molecular orbital (LUMO) of electrophile FST₂⁻ anion. In particular, the significant π–π stacking interactions of the low-energy pre-reaction state are retained in the lowest energy pathway for C–C coupling. The distortion/interaction–activation strain analysis indicates that the transition state (TScp-I) of the lowest energy pathway involves the highest stabilizing interactions and small distortion among all possible C–C coupling reactions. One of the two chiral centers generated in this step is lost upon aromatization of the phenol ring in the final difluostatin products. Thus, the π–π stacking interactions between the fluostatin 6-5-6 aromatic ring system play a critical role in the stereoselectivity of the nonenzymatic fluostatin conjugation. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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16 pages, 2181 KiB

Open AccessArticle

C-Methylation of S-adenosyl-L-Methionine Occurs Prior to Cyclopropanation in the Biosynthesis of 1-Amino-2-Methylcyclopropanecarboxylic Acid (Norcoronamic Acid) in a Bacterium

by Chitose Maruyama, Yukiko Chinone, Shusuke Sato, Fumitaka Kudo, Kosuke Ohsawa, Junya Kubota, Junko Hashimoto, Ikuko Kozone, Takayuki Doi, Kazuo Shin-ya, Tadashi Eguchi and Yoshimitsu Hamano

Biomolecules 2020, 10(5), 775; https://doi.org/10.3390/biom10050775 - 16 May 2020

Cited by 12 | Viewed by 3982

Abstract

Many pharmacologically important peptides are bacterial or fungal in origin and contain nonproteinogenic amino acid (NPA) building blocks. Recently, it was reported that, in bacteria, a cyclopropane-containing NPA 1-aminocyclopropanecarboxylic acid (ACC) is produced from the L-methionine moiety of S-adenosyl-L-methionine (SAM) by non-canonical [...] Read more.

Many pharmacologically important peptides are bacterial or fungal in origin and contain nonproteinogenic amino acid (NPA) building blocks. Recently, it was reported that, in bacteria, a cyclopropane-containing NPA 1-aminocyclopropanecarboxylic acid (ACC) is produced from the L-methionine moiety of S-adenosyl-L-methionine (SAM) by non-canonical ACC-forming enzymes. On the other hand, it has been suggested that a monomethylated ACC analogue, 2-methyl-ACC (MeACC), is derived from L-valine. Therefore, we have investigated the MeACC biosynthesis by identifying a gene cluster containing bacterial MeACC synthase genes. In this gene cluster, we identified two genes, orf29 and orf30, which encode a cobalamin (B12)-dependent radical SAM methyltransferase and a bacterial ACC synthase, respectively, and were found to be involved in the MeACC biosynthesis. In vitro analysis using their recombinant enzymes (rOrf29 and rOrf30) further revealed that the ACC structure of MeACC was derived from the L-methionine moiety of SAM, rather than L-valine. In addition, rOrf29 was found to catalyze the C-methylation of the L-methionine moiety of SAM. The resulting methylated derivative of SAM was then converted into MeACC by rOrf30. Thus, we demonstrate that C-methylation of SAM occurs prior to cyclopropanation in the biosynthesis of a bacterial MeACC (norcoronamic acid). Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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14 pages, 3510 KiB

Open AccessArticle

The Antitumor Agent Ansamitocin P-3 Binds to Cell Division Protein FtsZ in Actinosynnema pretiosum

by Xinran Wang, Rufan Wang, Qianjin Kang and Linquan Bai

Biomolecules 2020, 10(5), 699; https://doi.org/10.3390/biom10050699 - 30 Apr 2020

Cited by 9 | Viewed by 2738

Abstract

Ansamitocin P-3 (AP-3) is an important antitumor agent. The antitumor activity of AP-3 is a result of its affinity towards β-tubulin in eukaryotic cells. In this study, in order to improve AP-3 production, the reason for severe growth inhibition of the AP-3 producing [...] Read more.

Ansamitocin P-3 (AP-3) is an important antitumor agent. The antitumor activity of AP-3 is a result of its affinity towards β-tubulin in eukaryotic cells. In this study, in order to improve AP-3 production, the reason for severe growth inhibition of the AP-3 producing strain Actinosynnema pretiosum WXR-24 under high concentrations of exogenous AP-3 was investigated. The cell division protein FtsZ, which is the analogue of β-tubulin in bacteria, was discovered to be the AP-3 target through structural comparison followed by a SPR biosensor assay. AP-3 was trapped into a less hydrophilic groove near the GTPase pocket on FtsZ by hydrogen bounding and hydrophobic interactions, as revealed by docking analysis. After overexpression of the APASM_5716 gene coding for FtsZ in WXR-30, the resistance to AP-3 was significantly improved. Moreover, AP-3 yield was increased from 250.66 mg/L to 327.37 mg/L. After increasing the concentration of supplemented yeast extract, the final yield of AP-3 reached 371.16 mg/L. In summary, we demonstrate that the cell division protein FtsZ is newly identified as the bacterial target of AP-3, and improving resistance is an effective strategy to enhance AP-3 production. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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15 pages, 1664 KiB

Open AccessArticle

Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity

by Eunji Kim, Yern-Hyerk Shin, Tae Ho Kim, Woong Sub Byun, Jinsheng Cui, Young Eun Du, Hyung-Ju Lim, Myoung Chong Song, An Sung Kwon, Sang Hyeon Kang, Jongheon Shin, Sang Kook Lee, Jichan Jang, Dong-Chan Oh and Yeo Joon Yoon

Biomolecules 2019, 9(11), 672; https://doi.org/10.3390/biom9110672 - 30 Oct 2019

Cited by 15 | Viewed by 3676

Abstract

The cyclic depsipeptides ohmyungsamycin (OMS) A (1) and B (2), isolated from the marine-derived Streptomyces sp. SNJ042, contain two non-proteinogenic amino acid residues, β-hydroxy-l-phenylalanine (β-hydroxy-l-Phe) and 4-methoxy-l-tryptophan (4-methoxy-l-Trp). [...] Read more.

The cyclic depsipeptides ohmyungsamycin (OMS) A (1) and B (2), isolated from the marine-derived Streptomyces sp. SNJ042, contain two non-proteinogenic amino acid residues, β-hydroxy-l-phenylalanine (β-hydroxy-l-Phe) and 4-methoxy-l-tryptophan (4-methoxy-l-Trp). Draft genome sequencing of Streptomyces sp. SNJ042 revealed the OMS biosynthetic gene cluster consisting of a nonribosomal peptide synthetase (NRPS) gene and three genes for amino acid modification. By gene inactivation and analysis of the accumulated products, we found that OhmL, encoding a P450 gene, is an l-Phe β-hydroxylase. Furthermore, OhmK, encoding a Trp 2,3-dioxygenase homolog, and OhmJ, encoding an O-methyltransferase, are suggested to be involved in hydroxylation and O-methylation reactions, respectively, in the biosynthesis of 4-methoxy-l-Trp. In addition, the antiproliferative and antituberculosis activities of the OMS derivatives dehydroxy-OMS A (4) and demethoxy-OMS A (6) obtained from the mutant strains were evaluated in vitro. Interestingly, dehydroxy-OMS A (4) displayed significantly improved antituberculosis activity and decreased cytotoxicity compared to wild-type OMS A. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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Review

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14 pages, 1245 KiB

Open AccessReview

Recent Advances in Microbial Production of cis,cis-Muconic Acid

by Sisun Choi, Han-Na Lee, Eunhwi Park, Sang-Jong Lee and Eung-Soo Kim

Biomolecules 2020, 10(9), 1238; https://doi.org/10.3390/biom10091238 - 25 Aug 2020

Cited by 40 | Viewed by 6662

Abstract

cis,cis-Muconic acid (MA) is a valuable C6 dicarboxylic acid platform chemical that is used as a starting material for the production of various valuable polymers and drugs, including adipic acid and terephthalic acid. As an alternative to traditional chemical processes, bio-based MA [...] Read more.

cis,cis-Muconic acid (MA) is a valuable C6 dicarboxylic acid platform chemical that is used as a starting material for the production of various valuable polymers and drugs, including adipic acid and terephthalic acid. As an alternative to traditional chemical processes, bio-based MA production has progressed to the establishment of de novo MA pathways in several microorganisms, such as Escherichia coli, Corynebacterium glutamicum, Pseudomonas putida, and Saccharomyces cerevisiae. Redesign of the metabolic pathway, intermediate flux control, and culture process optimization were all pursued to maximize the microbial MA production yield. Recently, MA production from biomass, such as the aromatic polymer lignin, has also attracted attention from researchers focusing on microbes that are tolerant to aromatic compounds. This paper summarizes recent microbial MA production strategies that involve engineering the metabolic pathway genes as well as the heterologous expression of some foreign genes involved in MA biosynthesis. Microbial MA production will continue to play a vital role in the field of bio-refineries and a feasible way to complement various petrochemical-based chemical processes. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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15 pages, 2181 KiB

Open AccessReview

Recent Advances in the Biosynthesis of Carbazoles Produced by Actinomycetes

by Masaya Kobayashi and Tomohisa Kuzuyama

Biomolecules 2020, 10(8), 1147; https://doi.org/10.3390/biom10081147 - 05 Aug 2020

Cited by 10 | Viewed by 3257

Abstract

Structurally diverse carbazole alkaloids are valuable due to their pharmaceutical properties and have been isolated from nature. Experimental knowledge on carbazole biosynthesis is limited. The latest development of in silico analysis of the biosynthetic gene clusters for bacterial carbazoles has allowed studies on [...] Read more.

Structurally diverse carbazole alkaloids are valuable due to their pharmaceutical properties and have been isolated from nature. Experimental knowledge on carbazole biosynthesis is limited. The latest development of in silico analysis of the biosynthetic gene clusters for bacterial carbazoles has allowed studies on the biosynthesis of a carbazole skeleton, which was established by sequential enzyme-coupling reactions associated with an unprecedented carbazole synthase, a thiamine-dependent enzyme, and a ketosynthase-like enzyme. This review describes the carbazole biosynthetic mechanism, which includes a key step in enzymatic formation of a tricyclic carbazole skeleton, followed by modifications such as prenylation and hydroxylation in the skeleton. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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18 pages, 1654 KiB

Open AccessReview

Regulation of Protein Post-Translational Modifications on Metabolism of Actinomycetes

by Chen-Fan Sun, Yong-Quan Li and Xu-Ming Mao

Biomolecules 2020, 10(8), 1122; https://doi.org/10.3390/biom10081122 - 29 Jul 2020

Cited by 13 | Viewed by 3735

Abstract

Protein post-translational modification (PTM) is a reversible process, which can dynamically regulate the metabolic state of cells through regulation of protein structure, activity, localization or protein–protein interactions. Actinomycetes are present in the soil, air and water, and their life cycle is strongly determined [...] Read more.

Protein post-translational modification (PTM) is a reversible process, which can dynamically regulate the metabolic state of cells through regulation of protein structure, activity, localization or protein–protein interactions. Actinomycetes are present in the soil, air and water, and their life cycle is strongly determined by environmental conditions. The complexity of variable environments urges Actinomycetes to respond quickly to external stimuli. In recent years, advances in identification and quantification of PTMs have led researchers to deepen their understanding of the functions of PTMs in physiology and metabolism, including vegetative growth, sporulation, metabolite synthesis and infectivity. On the other hand, most donor groups for PTMs come from various metabolites, suggesting a complex association network between metabolic states, PTMs and signaling pathways. Here, we review the mechanisms and functions of PTMs identified in Actinomycetes, focusing on phosphorylation, acylation and protein degradation in an attempt to summarize the recent progress of research on PTMs and their important role in bacterial cellular processes. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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14 pages, 773 KiB

Open AccessReview

Challenges and Advances in Genome Editing Technologies in Streptomyces

by Yawei Zhao, Guoquan Li, Yunliang Chen and Yinhua Lu

Biomolecules 2020, 10(5), 734; https://doi.org/10.3390/biom10050734 - 08 May 2020

Cited by 24 | Viewed by 4571

Abstract

The genome of Streptomyces encodes a high number of natural product (NP) biosynthetic gene clusters (BGCs). Most of these BGCs are not expressed or are poorly expressed (commonly called silent BGCs) under traditional laboratory experimental conditions. These NP BGCs represent an unexplored rich [...] Read more.

The genome of Streptomyces encodes a high number of natural product (NP) biosynthetic gene clusters (BGCs). Most of these BGCs are not expressed or are poorly expressed (commonly called silent BGCs) under traditional laboratory experimental conditions. These NP BGCs represent an unexplored rich reservoir of natural compounds, which can be used to discover novel chemical compounds. To activate silent BGCs for NP discovery, two main strategies, including the induction of BGCs expression in native hosts and heterologous expression of BGCs in surrogate Streptomyces hosts, have been adopted, which normally requires genetic manipulation. So far, various genome editing technologies have been developed, which has markedly facilitated the activation of BGCs and NP overproduction in their native hosts, as well as in heterologous Streptomyces hosts. In this review, we summarize the challenges and recent advances in genome editing tools for Streptomyces genetic manipulation with a focus on editing tools based on clustered regularly interspaced short palindrome repeat (CRISPR)/CRISPR-associated protein (Cas) systems. Additionally, we discuss the future research focus, especially the development of endogenous CRISPR/Cas-based genome editing technologies in Streptomyces. Full article

(This article belongs to the Special Issue Recent Advance of Actinomycetes)

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