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] State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, P.O. Box 329#, 130 Meilong Rd., Shanghai 200237, China; [2] Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, HW623, 161 Cathedral Street, Glasgow G4 0RE, Scotland, United Kingdom

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：EI(收录号：20112214017610)

语种：英文

外文关键词：Biochemistry - Gene expression - Metabolic engineering - Carbon - Ketones - Bacteria - Biomolecules - Biosynthesis - Enzymes - Glucose - Physiology - Metabolites - Antibiotics

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. ? 2011 Elsevier Inc.