Reconstruction of the Saccharopolyspora erythraea genome-scale model and its use for enhancing erythromycin production

Cuauhtemoc Licona-Cassani, Esteban Marcellin, Lake Ee Quek, Shana Jacob, Lars K. Nielsen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Genome-scale metabolic reconstructions are routinely used for the analysis and design of metabolic engineering strategies for production of primary metabolites. The use of such reconstructions for metabolic engineering of antibiotic production is not common due to the lack of simple design algorithms in the absence of a cellular growth objective function. Here, we present the metabolic network reconstruction for the erythromycin producer Saccharopolyspora ery-thraea NRRL23338. The model was manually curated for primary and secondary metabolism pathways and consists of 1,482 reactions (2,075 genes) and 1,646 metabolites. As part of the model validation, we explored the potential benefits of supplying amino acids and identified five amino acids compatible" with erythromycin production, whereby if glucose is supplemented with this amino acid on a carbon mole basis, the in silico model predicts that high erythromycin yield is possible without lowering biomass yield. Increased erythromycin titre was confirmed for four of the five amino acids, namely valine, isoleucine, threonine and proline. In bioreactor experiments, supplementation with 2.5 % carbon mole of valine increased the growth rate by 20 % and simultaneously the erythromycin yield on biomass by 50 %. The model presented here can be used as a framework for the future integration of high-throughput biological data sets in S. erythraea and ultimately to realise strain designs capable of increasing erythromycin production closer to the theoretical yield.

Original languageEnglish
Pages (from-to)493-502
Number of pages10
JournalAntonie van Leeuwenhoek, International Journal of General and Molecular Microbiology
Volume102
Issue number3
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

Fingerprint

Saccharopolyspora
Erythromycin
Genome
Metabolic Engineering
Amino Acids
Valine
Biomass
Carbon
Secondary Metabolism
Isoleucine
Bioreactors
Threonine
Growth
Metabolic Networks and Pathways
Proline
Computer Simulation
Anti-Bacterial Agents
Glucose

Keywords

  • Erythromycin
  • Genome-scale metabolic reconstruction
  • S. erythraea

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Reconstruction of the Saccharopolyspora erythraea genome-scale model and its use for enhancing erythromycin production. / Licona-Cassani, Cuauhtemoc; Marcellin, Esteban; Quek, Lake Ee; Jacob, Shana; Nielsen, Lars K.

In: Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology, Vol. 102, No. 3, 10.2012, p. 493-502.

Research output: Contribution to journalArticle

Licona-Cassani, Cuauhtemoc ; Marcellin, Esteban ; Quek, Lake Ee ; Jacob, Shana ; Nielsen, Lars K. / Reconstruction of the Saccharopolyspora erythraea genome-scale model and its use for enhancing erythromycin production. In: Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology. 2012 ; Vol. 102, No. 3. pp. 493-502.
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