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Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1

Paper ID Volume ID Publish Year Pages File Format Full-Text
31774 44837 2011 10 PDF Available
Title
Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1
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 25 mg/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.

► We identified the gene cluster for cytochalasin E/K in Aspergillus clavatus genome. ► Involvement of a PKS–NRPS gene (ccsA) was confirmed by targeted gene disruption. ► A biosynthetic route for cytochalasin E/K was proposed based on gene cluster analyses. ► Overexpression of the ccsR regulator gene improved cytochalasin production. ► Genome mining revealed ccs-like gene clusters among other sequenced fungal genomes.

Keywords
PKS–NRPS, polyketide synthase–nonribosomal peptide synthetase; PDA, potato dextrose agar; MEPA, malt extract peptone medium agar; CDD, Conserved Domain DatabaseCytochalasins; PKS–NRPS; Fungal megasynthetases; Targeted gene inactivation; Pathway-specific r
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Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 13, Issue 6, November 2011, Pages 723–732
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us