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Updated: Sep 23, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
A case study of evolutionary variability and determinism among type III polyketide synthases
Ya-Hui Chen1, Yijun Yan2, Tian Tian2,3
1Institute of Herbgenomics and Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Abstract:
Repeated evolution of the same enzymatic activity represents a powerful model of determinism across diverse lineages, yet its underlying evolutionary trajectories remain poorly understood. Here we identified three 3-oxo-glutaric acid (OGA)-forming type III polyketide synthases (PKSs) from Brassicaceae plants through in vitro enzyme assays. Structure-function analysis combined with comparative genomics indicates a strong correlation between OGA- and triacetic acid lactone (TAL)-forming activities during the evolution of these PKSs. An evolutionary change in a key active-site residue enables a functional switch from TAL-forming activity to OGA-forming activity. Intriguingly, further chalcone synthase activity assays and expanded exploration of PKSs from additional plant lineages suggest that OGA-forming PKSs may have evolved repeatedly from the intrinsic TAL-forming activity of chalcone synthases in a lineage-specific manner. This evolutionary feature may help explain the recurrent emergence of OGA-forming PKSs in vascular plants and provide insight into the trajectories underlying the independent evolution of homologous isoenzymes in plants.
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