Natural product chemistry

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; Chem. Sci, 2014, 5, 397-402

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.