Polyketide Synthases (PKSs) are large modular enzymes responsible for the production of numerous medically significant polyketides such as the antibiotic Erythromycin and the antitumor compound Epothilone. Each module of a PKS has its own self-contained catalytic machinery for elongating and chemically modifying a polyketide chain. Nature synthesizes elaborate polyketides by linking together individual PKS modules (each with its own catalytic function) in an assembly-line format. This proposal aims to take advantage of the modular arrangement of PKSs with the hope of synthesizing and discovering novel medically beneficial compounds. The goal of this proposal is to develop an in vitro system for the facile rearrangement and recombination of individual PKS modules. The ability to connect individual PKS modules, without disrupting their natural functions, presents the opportunity for the production and eventual screening of large combinatorial libraries of PKSs, each having the potential to produce novel polyketide compounds.
| Moffet, David A; Khosla, Chaitan; Cane, David E (2006) Modular polyketide synthases: Investigating intermodular communication using 6 deoxyerythronolide B synthase module 2. Bioorg Med Chem Lett 16:213-6 |
