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  • Title: Functional expression of the Aspergillus flavus PKS-NRPS hybrid CpaA involved in the biosynthesis of cyclopiazonic acid.
    Author: Seshime Y, Juvvadi PR, Tokuoka M, Koyama Y, Kitamoto K, Ebizuka Y, Fujii I.
    Journal: Bioorg Med Chem Lett; 2009 Jun 15; 19(12):3288-92. PubMed ID: 19410456.
    Abstract:
    alpha-Cyclopiazonic acid (CPA) is an indole tetramic acid mycotoxin. Based on our identification of the polyketide synthase-nonribosomal peptide synthase (PKS-NRPS) hybrid gene cpaA involved in cyclopiazonic acid biosynthesis in Aspergillus fungi, we carried out heterologous expression of Aspergillus flavuscpaA under alpha-amylase promoter in Aspergillus oryzae and identified its sole product to be the CPA biosynthetic intermediate cyclo-acetoacetyl-l-tryptophan (cAATrp). This result rationalized that the PKS-NRPS hybrid enzyme CpaA catalyzes condensation of the diketide acetoacetyl-ACP formed by the PKS module and l-Trp activated by the NRPS module. This CpaA expression system provides us an ideal platform for PKS-NRPS functional analysis, such as adenylation domain selectivity and product releasing mechanism.
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