Dissecting and exploiting intermodular communication in polyketide synthases.

R S Gokhale; S Y Tsuji; D E Cane; C Khosla

doi:10.1126/science.284.5413.482

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PubMed · 10205055

Dissecting and exploiting intermodular communication in polyketide synthases.

R S Gokhale·S Y Tsuji·D E Cane·C Khosla

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Abstract

Modular polyketide synthases catalyze the biosynthesis of medicinally important natural products through an assembly-line mechanism. Although these megasynthases display very precise overall selectivity, we show that their constituent modules are remarkably tolerant toward diverse incoming acyl chains. By appropriate engineering of linkers, which exist within and between polypeptides, it is possible to exploit this tolerance to facilitate the transfer of biosynthetic intermediates between unnaturally linked modules. This protein engineering strategy also provides insights into the evolution of modular polyketide synthases.

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Amino Acid Sequence Catalysis Escherichia coli Evolution, Molecular Genes, Bacterial Lactones Macrolides Molecular Sequence Data Multienzyme Complexes Nuclear Magnetic Resonance, Biomolecular Peptides Protein Engineering Recombinant Fusion Proteins Streptomyces Journal Article Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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R S Gokhale, S Y Tsuji, D E Cane, C Khosla. 1999-04-16. Dissecting and exploiting intermodular communication in polyketide synthases.. https://doi.org/10.1126/science.284.5413.482

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