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Heterologous Biosynthesis of Type II Polyketide Products Using E. coli
Version 2 2020-03-05, 18:14
Version 1 2019-12-16, 05:31
journal contribution
posted on 2020-03-05, 18:14 authored by Xiangyang Liu, Kangmin Hua, Dongxu Liu, Zhen-Long Wu, Ying Wang, Haoran Zhang, Zixin Deng, Blaine A. Pfeifer, Ming JiangThe
heterologous biosynthesis of complex natural products has enabled
access to polyketide, nonribosomal peptide, isoprenoid, and other
compounds with wide-spanning societal value. Though several surrogate
host systems exist, Escherichia coli is often a preferred
choice due to its rapid growth kinetics and extensive molecular biology
protocols. However, a persistent challenge to the utilization of E. coli has been the successful in vivo reconstitution of type II polyketide synthase (PKS) systems. In
particular, gene expression of the ketosynthase (KS) components of
the minimal PKS has consistently yielded insoluble protein products.
In the following report, two type II PKS systems were functionally
reconstituted in E. coli. The approach to do so relied
upon the utilization of the native transcriptional coupling between
the dimeric KS subunits, leading to soluble recombinant protein products
and successful polyketide biosynthesis. Resulting strains produced
10 mg/L TW95c and 25 mg/L dehydrorabelomycin. Hence, the strategy
offers a new option in the biosynthetic engineering efforts for the
heterologous production of type II polyketide products using E. coli.