Engineering of Plant Polyketide Synthases

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  • Abe Ikuro
    School of Pharmaceutical Sciences , University of Shizuoka, and PRESTO, Japan Science and Technology Agency

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  • 植物ポリケタイド合成酵素の触媒機能の制御
  • ショクブツ ポリケタイド ゴウセイ コウソ ノ ショクバイ キノウ ノ セイギョ

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Abstract

Recent progress of our research on the plant-specific type III polyketide synthases (PKSs) is described. First, our studies demonstrated that the enzymes accept a variety of substrate analogues to synthesize products chemically and structurally different from the natural products. Manipulation of the enzymes by artificial substrates could thus lead to development of a chemical library of pharmaceutically important novel polyketides. Second, a growing number of functionally divergent type III PKSs have been cloned and characterized, which include recently obtained pentaketide chromone synthase and octaketide synthase from the aloe plant. Structure function analysis revealed that a chemically inert single residue lining the active-site cavity determines the polyketide chain length and the product specificity. The functional diversity of type III PKSs is thus evolved from the simple steric modulation of the active-site cavity accompanied by conservation of a Cys-His-Asn catalytic triad. These results provided novel strategies for the engineered biosynthesis of plant polyketides.

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