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 Characterisation and heterologous biosynthesis of burnettiene A, a new polyene-decalin polyketide from Aspergillus burnettii

2021 ◽  
Author(s):  
Indra Roux ◽  
Simon Bowles ◽  
John A. Kalaitzis ◽  
Daniel Vuong ◽  
Ernest Lacey ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Bioinformatic Analysis ◽  
Biosynthetic Gene Cluster ◽  
Tricarboxylic Acid ◽  
In Vitro Cytotoxicity ◽  
Methyl Groups ◽  
Biosynthetic Gene ◽  
Heterologous Biosynthesis ◽  
Mouse Myeloma

Chemical exploration of the recently described Australian fungus, Aspergillus burnettii, uncovered a new metabolite, burnettiene A. Here, we characterise the structure of burnettiene A as a polyene-decalin polyketide. Bioinformatic analysis of the genome of A. burnettii identified a putative biosynthetic gene cluster for burnettiene A (bue), consisting of eight genes and sharing similarity to the fusarielin gene cluster. Introduction of the reassembled bue gene cluster into Aspergillus nidulans for heterologous expression resulted in the production of burnettiene A under native promoters. Omission of bueE encoding a cytochrome P450 led to the production of preburnettiene A, confirming that BueE is responsible for catalysing the regiospecific multi-oxidation of terminal methyl groups to carboxylic acids. Similarly, bueF was shown to encode an ester-forming methyltransferase, with its omission resulting in the production of the tricarboxylic acid, preburnettiene B. Introduction of an additional copy of the transcription factor bueR under the regulation of the gpdA promoter significantly improved the heterologous production of the burnettienes. Burnettiene A displayed strong in vitro cytotoxicity against mouse myeloma NS-1 cells (MIC 0.8 µg/mL).

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 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.

Heterologous production of bisucaberin using a biosynthetic gene cluster cloned from a deep sea metagenome

2012 ◽  
Vol 8 (2) ◽  
pp. 482-485 ◽  
Author(s):  
Masaki J. Fujita ◽  
Nobutada Kimura ◽  
Hisayoshi Yokose ◽  
Masami Otsuka
Keyword(s):  
Gene Cluster ◽  
Deep Sea ◽  
Biosynthetic Gene Cluster ◽  
Heterologous Production ◽  
Biosynthetic Gene
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