Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 129, Issue 35, Pages 10642-+Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja074865p
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Funding
- NIGMS NIH HHS [R01 GM075857, R01-GM75857, R01 GM075857-01] Funding Source: Medline
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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-l-methyl-12H -benzo[b]xanthen12-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 domairis and offers significant opportunity toward the enzymatic synthesis of additional compounds.
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