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Updated: Nov 22, 2025

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Challenges of functional expression of complex polyketide biosynthetic gene clusters
Yaojie Gao1, Yuchun Zhao1, Xinyi He1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, PR China.
Abstract:
Polyketide natural products are valuable sources of bioactive molecules such as nutraceuticals and pharmaceuticals. The tremendous development of the genome sequence database revealed that the majority of the biosynthetic gene clusters (BGCs) are cryptic. Activation of these cryptic BGCs and identification of the related products is essential for finding more lead compounds for pharmaceuticals. On the other hand, 99% of microbes in nature cannot be cultured in regular conditions, which greatly hinders the efforts to explore their biosynthetic potentials. Expression of polyketide BGCs in heterologous hosts with better growth, good genetic characteristics, and amenable molecular tools is a robust approach to identify new polyketides and characterize their biosynthesis. This review outlines the challenges in the heterologous production of polyketide BGCs of bacterial origins.
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