Methods for making polyketides
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsChaitan Khosla, Janice Lau, Nicola L. Pohl
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Abstract
The stereochemical centers of a polyketide can be changed by replacement of ketosynthase domains in the polyketide synthase (PKS) enzyme that produces the polyketide. The specificity of the AT domains of a PKS is determined by a hypervariable region that can be replaced or altered to change the specificity of the AT domain from a naturally occurring extender unit to another naturally or non-naturally occurring extender unit. Non-naturally occurring extender units, including methylmalonyl N-acetyl cysteamine thioester can be incorporated into polyketides in recombinant host cells or in cell-free systems to make polyketides.
Claims7
A method of producing a polyketide with an inverted chirality at a chiral center generated by the incorporation of α-substituted malonyl extender unit, which method comprises obtaining a polyketide synthase in which the ketosynthase (KS) domain responsible for generating said chiral center is substituted with a second KS domain that generates the opposite chirality in a polyketide synthase module.
Dependencies are inferred from the claim text.