Structures and Functional Analyses of Fungal Polyketide Synthase Genes

Abstract

Polyketide synthase (PKS) genes have been cloned from several fungi, such as Penicillium patulum MSAS, Aspergillus terreus atX and TPKS, Colletotrichum lagenarium PKS1, Aspergillus nidulans wA and stcA, Aspergillus parasiticus pksA, Cochliobolus heterostrophus CH-PKS1. Their coded PKSs all belong to type I of multifunctional enzymes. In contrast to bacterial type I PKS of modular type, fungal PKSs are of iterative type and classified into three groups: A) single aromatic ring PKS, B) multi-aromatic ring PKS, and C) reduced complex-type PKS. To confirm actual function of fungal PKSs, atX, PKS1, and wA genes were expressed in heterologous fungi with the amyB controlled fungal expression system. Their product compounds were identified to be 6- methylsalicylic acid (1), 1,3,6,8-tetrahydroxynaphthalene (3), and naphthopyrone compound YWA1 (15), respectively. Modification of C-terminal region of WA PKS caused shift of product from YWA1 (15) to the same heptaketide compound citreoisocoumarin (14). This result indicated that domains previously designated as thioesterase of group B PKSs function as Claisen-type cyclase.