scholarly journals Trichoderma reesei Contains a Biosynthetic Gene Cluster That Encodes the Antifungal Agent Ilicicolin H

2021 ◽  
Vol 7 (12) ◽  
pp. 1034
Author(s):  
Mary L. Shenouda ◽  
Maria Ambilika ◽  
Russell J. Cox
Keyword(s):  
Cytochrome P450 ◽  
Gene Cluster ◽  
Trichoderma Reesei ◽  
Antifungal Agent ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Fungal Host ◽  
Tetramic Acids ◽  
New Compounds

The trili biosynthetic gene cluster (BGC) from the well-studied organism Trichoderma reesei was studied by heterologous expression in the fungal host Aspergillus oryzae. Coexpression of triliA and triliB produces two new acyl tetramic acids. Addition of the ring-expanding cytochrome P450 encoded by triliC then yields a known pyridone intermediate to ilicicolin H and a new chain-truncated shunt metabolite. Finally, addition of the intramolecular Diels-Alderase encoded by triliD affords a mixture of 8-epi ilicicolin H and ilicicolin H itself, showing that the T. reesei trili BGC encodes biosynthesis of this potent antifungal agent. Unexpected A. oryzae shunt pathways are responsible for the production of the new compounds, emphasising the role of fungal hosts in catalysing diversification reactions.

scholarly journals Bioactive Molecules from Mangrove Streptomyces qinglanensis 172205

Marine Drugs ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. 255
Author(s):  
Dongbo Xu ◽  
Erli Tian ◽  
Fandong Kong ◽  
Kui Hong
Keyword(s):  
Gene Cluster ◽  
Secondary Metabolite ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Spectroscopic Methods ◽  
Biosynthetic Gene ◽  
Electronic Circular Dichroism ◽  
Chemical Structures ◽  
New Compounds ◽  
Antiproliferative Activities

Five new compounds 15R-17,18-dehydroxantholipin (1), (3E,5E,7E)-3-methyldeca-3,5,7-triene-2,9-dione (2) and qinlactone A–C (3–5) were identified from mangrove Streptomyces qinglanensis 172205 with “genetic dereplication,” which deleted the highly expressed secondary metabolite-enterocin biosynthetic gene cluster. The chemical structures were established by spectroscopic methods, and the absolute configurations were determined by electronic circular dichroism (ECD). Compound 1 exhibited strong anti-microbial and antiproliferative bioactivities, while compounds 2–4 showed weak antiproliferative activities.

scholarly journals Heterologous Biosynthesis and Genomics-Driven Derivatization of Fungal Bioactive Sesterterpenoid Variecolin

2021 ◽  
Author(s):  
Dexiu Yan ◽  
Jemma Arakelyan ◽  
Teng Wan ◽  
Tsz Ki Chan ◽  
Dohyun Ahn ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Anticancer Activity ◽  
Gene Cluster ◽  
Aspergillus Oryzae ◽  
Biosynthetic Gene Cluster ◽  
Heterologous Production ◽  
Biosynthetic Gene ◽  
Aspergillus Aculeatus ◽  
Heterologous Biosynthesis

The biosynthetic gene cluster of fungal bioactive sesterterpenoids, variecolin (1) and variecolactone (2), was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues, one of which exhibited potent anticancer activity comparable to that of 1.

scholarly journals Characterization of two cytochrome P450 monooxygenase genes of the pyripyropene biosynthetic gene cluster from Penicillium coprobium

2011 ◽  
Vol 64 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Jie Hu ◽  
Hiroto Okawa ◽  
Kentaro Yamamoto ◽  
Kazuhiko Oyama ◽  
Masaaki Mitomi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Cytochrome P450 Monooxygenase ◽  
Biosynthetic Gene ◽  
P450 Monooxygenase

scholarly journals Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ying Ma ◽  
Guanghong Cui ◽  
Tong Chen ◽  
Xiaohui Ma ◽  
Ruishan Wang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Gene Cluster ◽  
Genome Assembly ◽  
Salvia Miltiorrhiza ◽  
Gene Array ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Chinese Medicinal Herb ◽  
Gene Expansion ◽  
Homozygous Genotype

AbstractTanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.

scholarly journals Organization of the biosynthetic gene cluster for the macrolide concanamycin A in Streptomyces neyagawaensis ATCC 27449

Microbiology ◽  
2005 ◽  
Vol 151 (10) ◽  
pp. 3161-3169 ◽  
Author(s):  
Stephen F. Haydock ◽  
Anthony N. Appleyard ◽  
Tatiana Mironenko ◽  
John Lester ◽  
Natasha Scott ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
Polyketide Synthase ◽  
Building Blocks ◽  
Biosynthetic Gene Cluster ◽  
Sequence Motif ◽  
Biosynthetic Gene ◽  
Concanamycin A ◽  
Modular Polyketide Synthase

The macrolide antibiotic concanamycin A has been identified as an exceptionally potent inhibitor of the vacuolar (V-type) ATPase. Such compounds have been mooted as the basis of a potential drug treatment for osteoporosis, since the V-ATPase is involved in the osteoclast-mediated bone resorption that underlies this common condition. To enable combinatorial engineering of altered concanamycins, the biosynthetic gene cluster governing the biosynthesis of concanamycin A has been cloned from Streptomyces neyagawaensis and shown to span a region of over 100 kbp of contiguous DNA. An efficient transformation system has been developed for S. neyagawaensis and used to demonstrate the role of the cloned locus in the formation of concanamycin A. Sequence analysis of the 28 ORFs in the region has revealed key features of the biosynthetic pathway, in particular the biosynthetic origin of portions of the backbone, which arise from the unusual polyketide building blocks ethylmalonyl-CoA and methoxymalonyl-ACP, and the origin of the pendant deoxysugar moiety 4′-O-carbamoyl-2′-deoxyrhamnose, as well as the presence of a modular polyketide synthase (PKS) encoded by six giant ORFs. Examination of the methoxymalonyl-specific acyltransferase (AT) domains has led to recognition of an amino acid sequence motif which can be used to distinguish methylmalonyl-CoA- from methoxymalonyl-ACP-specific AT domains in natural PKSs.

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