文献类型：期刊文献

英文题名：Improved oxytetracycline production in Streptomyces rimosus M4018 by metabolic engineering of the G6PDH gene in the pentose phosphate pathway

作者：Tang, Zhenyu[1];Xiao, Ciying[1];Zhuang, Yingping[1];Chu, Ju[1];Zhang, Siliang[1];Herron, Paul R.[2];Hunter, Iain S.[2];Guo, Meijin[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0RE, Lanark, Scotland

年份：2011

卷号：49

期号：1

起止页码：17

外文期刊名：ENZYME AND MICROBIAL TECHNOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000292231500004)】；

基金：This work was supported by grants from the National High Technology and Development Program of China (2007AA100601), Outstanding Youth talent plan of ECUST and the National Special Fund for State Key Laboratory of Bioreactor Engineering (No. 2060204).

语种：英文

外文关键词：Glucose-6-phosphate dehydrogenase; Streptomyces rimosus M4018; Oxytetracycline biosynthesis; NADPH generation; Malonyl-CoA

摘要：The aromatic polyketide antibiotic, oxytetracycline (OTC), is produced by Streptomyces rimosus as an important secondary metabolite. High level production of antibiotics in Streptomycetes requires precursors and cofactors which are derived from primary metabolism; therefore it is exigent to engineer the primary metabolism. This has been demonstrated by targeting a key enzyme in the oxidative pentose phosphate pathway (PPP) and nicotinamide adenine dinucleotide phosphate (NADPH) generation, glucose-6-phosphate dehydrogenase (G6PDH), which is encoded by zwf1 and zwf2. Disruption of zwf1 or zwf2 resulted in a higher production of OTC. The disrupted strain had an increased carbon flux through glycolysis and a decreased carbon flux through PPP, as measured by the enzyme activities of G6PDH and phosphoglucose isomerase (PGI), and by the levels of ATP, which establishes G6PDH as a key player in determining carbon flux distribution. The increased production of OTC appeared to be largely due to the generation of more malonyl-CoA, one of the OTC precursors, as observed in the disrupted mutants. We have studied the effect of zwf modification on metabolite levels, gene expression, and secondary metabolite production to gain greater insight into flux distribution and the link between the fluxes in the primary and secondary metabolisms. (C) 2011 Elsevier Inc. All rights reserved.