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

27 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.
LanguageEnglish
Pages17-24
Number of pages8
JournalEnzyme and Microbial Technology
Volume49
Issue number1
DOIs
Publication statusPublished - 10 Jun 2011

Fingerprint

Streptomyces rimosus
Metabolic engineering
Metabolic Engineering
Pentoses
Pentose Phosphate Pathway
Oxytetracycline
Glucosephosphate Dehydrogenase
Carbon Cycle
Genes
Phosphates
Fluxes
Glucose-6-Phosphate Isomerase
Metabolites
Carbon
Metabolism
Malonyl Coenzyme A
Secondary Metabolism
Anti-Bacterial Agents
Polyketides
Glycolysis

Keywords

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

Cite this

Tang, Zhenyu ; Xiao, Ciying ; Zhuang, Yingping ; Chu, Ju ; Zhang, Siliang ; Herron, Paul ; Hunter, Iain ; Meijin, Guo. / Improved oxytetracycline production in Streptomyces rimosus M4018 by metabolic engineering of the G6PDH gene in the pentose phosphate pathway. In: Enzyme and Microbial Technology. 2011 ; Vol. 49, No. 1. pp. 17-24.
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Improved oxytetracycline production in Streptomyces rimosus M4018 by metabolic engineering of the G6PDH gene in the pentose phosphate pathway. / Tang, Zhenyu; Xiao, Ciying; Zhuang, Yingping; Chu, Ju; Zhang, Siliang; Herron, Paul; Hunter, Iain; Meijin, Guo.

In: Enzyme and Microbial Technology, Vol. 49, No. 1, 10.06.2011, p. 17-24.

Research output: Contribution to journalArticle

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AU - Tang, Zhenyu

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