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 Engjournal_title
Metabolic engineeringauthors
Qiao K,Chooi YH,Tang Ydoi
10.1016/j.ymben.2011.09.008subject
Has Abstractpub_date
2011-11-01 00:00:00pages
723-32issue
6eissn
1096-7176issn
1096-7184pii
S1096-7176(11)00098-Xjournal_volume
13pub_type
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journal_title:Metabolic engineering
pub_type: 杂志文章,评审
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