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

Zhenyu Tang, Ciying Xiao, Yingping Zhuang, Ju Chu, Siliang Zhang, Paul Herron, Iain Hunter, Guo Meijin

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalEnzyme and Microbial Technology
Volume49
Issue number1
DOIs
Publication statusPublished - 10 Jun 2011

Keywords

  • glucose-6-phosphate dehydrogenase
  • malonyl-CoA
  • NADPH generation
  • oxytetracycline biosynthesis
  • streptomyces rimosus M4018

Fingerprint Dive into the research topics of 'Improved oxytetracycline production in Streptomyces rimosus M4018 by metabolic engineering of the G6PDH gene in the pentose phosphate pathway'. Together they form a unique fingerprint.

  • Cite this