Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro

	Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro
	Keasling, JD; Curran, SC; Hagen, A; Poust, S; Chan, LLG; Garabedian, BM; de Rond, T; Baluyot, MJ; Vu, JT; Lau, AK
刊名	ACS CHEMICAL BIOLOGY
	2018
文献子类	期刊论文
英文摘要	In the search for molecular machinery for custom biosynthesis of valuable compounds, the modular type I polyketide synthases (PKSs) offer great potential. In this study, we investigate the flexibility of BorM5, the iterative fifth module of the borrelidin synthase, with a panel of non-native priming substrates in vitro. BorM5 differentially extends various aliphatic and substituted substrates. Depending on substrate size and substitution BorM5 can exceed the three iterations it natively performs. To probe the effect of methyl branching on chain length regulation, we engineered a BorM5 variant capable of incorporating methylmalonyl- and malonyl-CoA into its intermediates. Intermediate methylation did not affect overall chain length, indicating that the enzyme does not to count methyl branches to specify the number of iterations. In addition to providing regulatory insight about BorM5, we produced dozens of novel methylated intermediates that might be used for production of various hydrocarbons or pharmaceuticals. These findings enable rational engineering and recombination of BorM5 and inform the study of other iterative modules.
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/13447]
专题	合成所
推荐引用方式 GB/T 7714	Keasling, JD,Curran, SC, Hagen, A,et al. Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro[J]. ACS CHEMICAL BIOLOGY,2018.
APA	Keasling, JD.,Curran, SC., Hagen, A.,Poust, S.,Chan, LLG.,...&Katz, L.(2018).Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro.ACS CHEMICAL BIOLOGY.
MLA	Keasling, JD,et al."Probing the Flexibility of an Iterative Modular Polyketide Synthase with Non-Native Substrates in Vitro".ACS CHEMICAL BIOLOGY (2018).