ArticleMetabolic engineering2011
Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1.
Article in Metabolic engineering, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58 citing papers in PubMed, 139 citations in OpenAlex.
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- Structure and Biosynthesis of Perochalasins A-C, Open-Chain Merocytochalasans Produced by the Marine-Derived FungusJournal of natural products · 2024Article
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- Genome analysis of Cephalotrichum gorgonifer and identification of the biosynthetic pathway for rasfonin, an inhibitor of KRAS dependent cancer.Fungal biology and biotechnology · 2023Article
- Enhanced production of aspochalasin D through genetic engineering of Aspergillus flavipes.Applied microbiology and biotechnology · 2023Article
- Biosynthesis of the Isocoumarin Derivatives Fusamarins is Mediated by the PKS8 Gene Cluster in Fusarium.Chembiochem : a European journal of chemical biology · 2023Article
- Six Unprecedented Cytochalasin Derivatives from the Potato Endophytic FungusPharmaceuticals (Basel, Switzerland) · 2023Article
- Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining.Natural product reports · 2023Review
- Genome-Based Analysis ofBiology · 2022Article
- Cytochalasans from the Endophytic FungusJournal of fungi (Basel, Switzerland) · 2022Article
- Berberine bridge enzyme-like oxidase-catalysed double bond isomerization acts as the pathway switch in cytochalasin synthesis.Nature communications · 2022Article
- Synthaser: a CD-Search enabled Python toolkit for analysing domain architecture of fungal secondary metabolite megasynth(et)ases.Fungal biology and biotechnology · 2021Article
- Discovery and investigation of natural Diels-Alderases.Journal of natural medicines · 2021Review
- Catalytic mechanism andNature catalysis · 2021Article
- Chemical and Genetic Studies on the Formation of Pyrrolones During the Biosynthesis of Cytochalasans.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Transcriptome analysis implicates secondary metabolite production, redox reactions, and programmed cell death during allorecognition in Cryphonectria parasitica.G3 (Bethesda, Md.) · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a producer of cytochalasin E and K, the genome of A. clavatus was analyzed and the ∼30 kb ccs gene cluster was identified based on the presence of a polyketide synthase-nonribosomal peptide synthetases (PKS-NRPS) and a putative Baeyer-Villiger monooxygenase (BVMO). Deletion of the central PKS-NRPS gene, ccsA, abolished the production of cytochalasin E and K, confirming the association between the natural products and the gene cluster. Based on bioinformatic analysis, a putative biosynthetic pathway is proposed. Furthermore, overexpression of the pathway specific regulator ccsR elevated the titer of cytochalasin E from 25mg/L to 175 mg/L. Our results not only shed light on the biosynthesis of cytochalasins, but also provided genetic tools for increasing and engineering the production.
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