1887

Abstract

Type I polyketide synthases (PKSs) are complexes of large, multimodular enzymes that catalyse biosynthesis of polyketide compounds via repetitive reaction sequences, during which each step is catalysed by a separate enzymic domain. Many type I PKSs, and also non-ribosomal peptide synthetase clusters, contain additional thioesterase genes located adjacent to PKS genes. These are discrete proteins called type II thioesterases (TE IIs) to distinguish them from chain-terminating thioesterase (TE I) domains that are usually fused to the terminal PKS module. A gene of a new TE II, , associated with the cluster of putative type I PKS genes from A3(2), was found. The deduced amino acid sequence of the gene product shows extensive similarity to other authentic thioesterase enzymes, including conservation of characteristic motifs and residues involved in catalysis. When expressed in the heterologous host , successfully complemented the resident TE II gene (), and, by restoring a significant level of macrolide production, proved to be catalytically equivalent to the TylO protein. S nuclease mapping of revealed a single potential transcription start point with expression being switched on for a short period of time during a transition phase of growth.

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2002-06-01
2024-03-29
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