Structure and biosynthetic implication of (S)-NHAB, a novel shunt product, from a disruptant of the actVI-ORFA gene for actinorhodin biosynthesis in Streptomyces coelicolor A3(2)

Makoto Ozawa, Takaaki Taguchi, Takayuki Itoh, Yutaka Ebizuka, Kevin I. Booker-Milburn, G. Richard Stephenson, Koji Ichinose

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A novel shunt product was isolated from a disruptant of the actVI-ORFA gene involved in the biosynthesis of actinorhodin (ACT) in Streptomyces coelicolor A3(2). Its structure was elucidated as 1,4-naphthoquinone-8-hydroxy-3-[3(S)-acetoxy-butyric acid], (S)-NHAB, based on NMR, MS. and CD spectroscopic data as well as a single crystal X-ray crystallographic analysis. The formation of (S)-NHAB involves a retro-Claisen type C-C bond cleavage of an ACT biosynthetic intermediate. Feeding experiments with [1-C-13] and [2-C-13] acetates indicated its biosynthetic origin as a single octaketide chain. The relevant gene product, Act-ORFA, which is a functionally unknown protein. is proposed to play a regulatory role related to the multi-enzymatic steps to ACT production, based on the metabolic profile of its disruptant and the wide distribution of actVI-ORFA homologues in the gene clusters for Streptomyces aromatic polyketides. (C) 2003 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)8793-8798
Number of pages6
JournalTetrahedron
Volume59
Issue number44
DOIs
Publication statusPublished - 2003

Cite this