Using chemobiosynthesis and synthetic mini-polyketide synthases to produce pharmaceutical intermediates in Escherichia coli.

ABSTRACT: Recombinant microbial whole-cell biocatalysis is a valuable approach for producing enantiomerically pure intermediates for the synthesis of complex molecules. Here, we describe a method to produce polyketide intermediates possessing multiple stereogenic centers by combining chemobiosynthesis and engineered mini-polyketide synthases (PKSs). Chemobiosynthesis allows the introduction of unnatural moieties, while a library of synthetic bimodular PKSs expressed from codon-optimized genes permits the introduction of a variety of ketide units. To validate the approach, intermediates for the synthesis of trans-9,10-dehydroepothilone D were generated. The designer molecules obtained have the potential to greatly reduce the manufacturing cost of epothilone analogues, thus facilitating their commerci

SUBMITTER: Menzella HG 

PROVIDER: S-EPMC2916480 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature