Web Release Date: August 14,
Enzymatic Synthesis of Aromatic Polyketides Using PKS4 from Gibberella fujikuroi
and
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, and Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089
Received July 16, 2007
Abstract:
Iterative fungal polyketide synthases (PKSs) use a unique set of biochemical rules in the synthesis of complex polyketides. These rules dictate polyketide starter unit selection, chain length control, and post-PKS processing. We have demonstrated the E. coli expression and reconstitution of an iterative, unreduced fungal PKS. The Gibberella fujikuroi PKS4 was expressed at high levels, purified to homogeneity, and functionally characterized. In the presence of malonyl-CoA, PKS4 was able to synthesize the nonaketide 3,8,10,11-tetrahydroxy-1-methyl-12H-benzo[b]xanthen-12-one (2) as the predominant product. PKS4 selectively used octanoyl-CoA as the starter unit and synthesized two novel benzopyrone-containing polyketides. Our work sets the stage for a comprehensive characterization of the intact PKS and its domains and offers significant opportunity toward the enzymatic synthesis of additional compounds.
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