A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis.

Type I polyketide synthases often use programmed β-branching, via enzymes of a 'hydroxymethylglutaryl-CoA synthase (HCS) cassette', to incorporate various side chains at the second carbon from the terminal carboxylic acid of growing polyketide backbones. We identified a strong sequence motif in acyl carrier proteins (ACPs) where β-branching is known to occur. Substituting ACPs confirmed a correlation of ACP type with β-branching specificity.

A natural plasmid uniquely encodes two biosynthetic pathways creating a potent anti-MRSA antibiotic.

Background: Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin.

Methodology/principal Findings: High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters.

Mupirocin: biosynthesis, special features and applications of an antibiotic from a gram-negative bacterium.

Mupirocin is a polyketide antibiotic produced by Pseudomonas fluorescens. The biosynthetic cluster encodes 6 type I polyketide synthase multifunctional proteins and 29 single function proteins. The biosynthetic pathway belongs to the trans-AT group in which acyltransferase activity is provided by a separate polypeptide rather than in-cis as found in the original type I polyketide synthases.