Analysis of the maximum theoretical yield for the synthesis of erythromycin precursors in Escherichia coli

Joanna González-Lergier, Linda J. Broadbelt, Vassily Hatzimanikatis*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The heterologous biosynthesis of complex polyketides in Escherichia coli was recently achieved through metabolic engineering. However, it was observed that less than 10% of the propionate carbon source is transformed into the erythromycin precursor, 6-deoxyerythronolide B (6dEB), resulting in a 1.4% molar yield. Therefore, metabolic flux analysis was performed using a model of the Escherichia coli metabolism with the addition of the enzymes required for 6dEB synthesis. The analysis shows that the maximum theoretical yield for 6dEB synthesis in E. coli is 11%. The maintenance energy requirement of E. coli and limitations in the specific oxygen uptake rate can further decrease the yield, suggesting that the observed 6dEB yield of 1.4% can be the result of these two factors. In addition, the results suggest that an increase in the specific carbon and oxygen uptake rates will increase the yield of 6dEB. The use of glucose as an alternative carbon source was also evaluated using metabolic flux analysis and the results suggest that the choice of glucose as the carbon source will allow a small improvement in performance relative to a propionate-based process.

Original languageEnglish (US)
Pages (from-to)638-644
Number of pages7
JournalBiotechnology and Bioengineering
Volume95
Issue number4
DOIs
StatePublished - Nov 5 2006

Keywords

  • 6-Deoxyerythronolide (6dEB) synthesis
  • Genome scale model
  • Heterologous antibiotic production
  • In silico pathway analysis
  • Linear optimization
  • Metabolic flux analysis

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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