Diversity-Oriented Combinatorial Biosynthesis of Hybrid Polyketide Scaffolds from Azaphilone and Benzenediol Lactone
Jing Bai1,2, Yuanyuan Lu2,3, Ya-ming Xu2
1Biotechnology Research Institute, The Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street, Beijing 100081, P. R. China.
Abstract:
Two disparate polyketide families, the benzenediol lactones and the azaphilones, are produced by fungi using iterative polyketide synthase (iPKS) enzymes consisting of collaborating partner subunits. Exploitation of this common biosynthetic logic using iPKS subunit shuffling allowed the diversity-oriented combinatorial biosynthesis of unprecedented polyketide scaffolds new to nature, bearing structural motifs from both of these orthogonal natural product families. Starter unit acyltransferase domain replacements proved necessary but not sufficient to guarantee communication between iPKS subunits.
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