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 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.

journal_name

Metab Eng

journal_title

Metabolic engineering

authors

Qiao K,Chooi YH,Tang Y

doi

10.1016/j.ymben.2011.09.008

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

723-32

issue

6

eissn

1096-7176

issn

1096-7184

pii

S1096-7176(11)00098-X

journal_volume

13

pub_type

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