Ren Jie, Zhou Libang, Wang Chuang, Lin Chen, Li Zhidong, Zeng An-Ping
Beijing Advanced Innovation Center for Soft Matter Science and Engineering , Beijing University of Chemical Technology , North Third Ring Road 15, Chaoyang District , 100029 , Beijing , China.
Institute of Bioprocess and Biosystems Engineering , Hamburg University of Technology , Denickestrasse 15 , D-21073 Hamburg , Germany.
ACS Synth Biol. 2018 Dec 21;7(12):2750-2757. doi: 10.1021/acssynbio.8b00354. Epub 2018 Nov 29.
The design of novel metabolic pathways for efficient biosynthesis of natural products has received much interest, but often lacks systematic approach and chemistry-based guideline. Here we propose carbon skeleton reconstruction based on retrobiosynthetic design as a new approach and chemistry-guideline to solve the problem of properly matching precursors, one of the key issues for efficient biosynthesis. It is demonstrated for the development of an unnatural pathway for efficient biosynthesis of 5-aminolevulinic acid. The new pathway has several advantages compared to the existing natural ones such as high carbon utilization efficiency and orthogonality. It is particularly useful for overcoming the problem of glycine supply. The unnatural pathway is verified in vitro in an enzymatic cascade and in vivo in recombinant E. coli with an exogenous glyoxylate transaminase as a key enzyme.
用于天然产物高效生物合成的新型代谢途径设计已备受关注，但往往缺乏系统方法和基于化学的指导原则。在此，我们提出基于逆生物合成设计的碳骨架重构作为一种新方法和化学指导原则，以解决前体正确匹配的问题，这是高效生物合成的关键问题之一。以开发5-氨基乙酰丙酸高效生物合成的非天然途径为例进行了说明。与现有的天然途径相比，新途径具有若干优势，如高碳利用效率和正交性。它对于克服甘氨酸供应问题特别有用。该非天然途径在体外通过酶级联反应得到验证，在体内通过以外源乙醛酸转氨酶为关键酶的重组大肠杆菌得到验证。
