Identification of genes encoding squalestatin S1 biosynthesis and in vitro production of new squalestatin analogues

B Bonsch, V Belt, C Bartel, N Duensing, M Koziol, C M Lazarus, A M Bailey, T J Simpson, R J Cox

Research output: Contribution to journalArticle (Academic Journal)peer-review

30 Citations (Scopus)
246 Downloads (Pure)

Abstract

A gene cluster responsible for the biosynthesis of squalestatin S1 (SQS1, 1) was identified by full genome sequencing of two SQS1-producing ascomycetes: Phoma sp. C2932 and unidentified fungus MF5453. A transformation protocol was established and a subsequent knockout of one PKS gene from the cluster led to loss of SQS1 production and enhanced concentration of an SQS1 precursor. An acyltransferase gene from the cluster was expressed in E. coli and the expressed protein MfM4 shown to be responsible for loading acyl groups from CoA onto the squalestatin core as the final step of biosynthesis. MfM4 appears to have a broad substrate selectivity for its acyl CoA substrate, allowing the in vitro synthesis of novel squalestatins.

Original languageEnglish
Pages (from-to)6777-6780
Number of pages4
JournalChemical Communications
Volume52
Issue number41
Early online date1 Apr 2016
DOIs
Publication statusPublished - 21 May 2016

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