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

Biotechnology and Bioengineering
Joanna González-LergierVassily Hatzimanikatis

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.

References

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Citations

Jan 15, 2008·Applied and Environmental Microbiology·Bruno BühlerAndreas Schmid
Feb 4, 2010·BMC Systems Biology·Stacey D FinleyVassily Hatzimanikatis
Jul 16, 2015·Current Opinion in Chemical Biology·Noushin Hadadi, Vassily Hatzimanikatis
Jun 5, 2020·Metabolites·R Axayacatl Gonzalez-GarciaEsteban Marcellin
Feb 1, 2008·Molecular Pharmaceutics·Haoran ZhangBlaine A Pfeifer

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