Biosynthesis of thiomarinol A and related metabolites of Pseudoalteromonas sp. SANK 73390

Annabel C. Murphy; Shu-Shan Gao; Li-Chen Han; Simon Carobene; Daisuke Fukuda; Zhongshu Song; Joanne Hothersall; Russell J. Cox; John Crosby; Matthew P. Crump; Christopher M. Thomas; Christine L. Willis; Thomas J. Simpson

doi:10.1039/C3SC52281D

Biosynthesis of thiomarinol A and related metabolites of Pseudoalteromonas sp. SANK 73390†

Annabel C. Murphy,‡§^a Shu-Shan Gao,‡^a Li-Chen Han,^a Simon Carobene,^a Daisuke Fukuda,^bc Zhongshu Song,^a Joanne Hothersall,^b Russell J. Cox,^a John Crosby,^a Matthew P. Crump,^a Christopher M. Thomas,^b Christine L. Willis*^a and Thomas J. Simpson*^a

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^a School of Chemistry, University of Bristol, Cantock's Close, Bristol, UK
E-mail: chris.willis@bristol.ac.uk, tom.simpson@bristol.ac.uk
Fax: +44 (0)117 925 1295
Tel: +44 (0)117 928 7660

^b School of Biosiences, University of Birmingham, Edgbaston, Birmingham, UK

^c Discovery Science and Technology Department, Daiichi Sankyo RD Novare co., Ltd, 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo, Japan

Abstract

The biosynthesis of the mixed PKS-FAS-NRPS hybrid antibiotic thiomarinol A was investigated using feeding studies to both wild type and mutant strains of the marine bacterium Pseudoalteromonas. Particularly interesting features of the pathway include assembly of the 8-hydroxyoctanoic acid side-chain via chain extension of a C₄-precursor (4-hydroxybutyrate), and construction of the pyrrothine unit from cysteine via (HolA-D, F-H) prior to intact incorporation into thiomarinol (catalysed by TmlU). A series of thiomarinol-related and other minor metabolites have been isolated from wild-type and mutant strains. The results of these investigations are rationalised in terms of the overall biosynthetic pathway.

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Chemical Science

Biosynthesis of thiomarinol A and related metabolites of Pseudoalteromonas sp. SANK 73390†

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Biosynthesis of thiomarinol A and related metabolites of Pseudoalteromonas sp. SANK 73390

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