Abstract
In carbohydrate-based fermentations of Saccharopolyspora erythraea, a polar knockout of the methylmalonyl-CoA mutase (MCM) gene, mutB, improved erythromycin production an average of 126% (within the range of 102–153% for a 0.95 confidence interval). In oil-based fermentations, where erythromycin production by the wild-type strain averages 184% higher (141–236%, 0.95 CI) than in carbohydrate-based fermentations, the same polar knockout in mutB surprisingly reduced erythromycin production by 66% (53–76%, 0.95 CI). A metabolic model is proposed where in carbohydrate-based fermentations MCM acts as a drain on the methylmalonyl-CoA metabolite pool, and in oil-based fermentations, MCM acts in the reverse direction to fill the methylmalonyl-CoA pool. Therefore, the model explains, in part, how the well-known oil-based process improvement for erythromycin production operates at the biochemical level; furthermore, it illustrates how the mutB erythromycin strain improvement mutation operates at the genetic level in carbohydrate-based fermentations.
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Acknowledgements
The authors thank Roy Wesley for helpful comments; Steven Wachs and Allise Wachs of Integral Concepts for helpful discussions and advice on statistical analyses; the National Institute of General Medical Sciences for financial support (Small Business Innovation Research Awards R44GM58943 and R44GM063278); and the John Innes Streptomyces Club for technical and material support.
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Reeves, A.R., Brikun, I.A., Cernota, W.H. et al. Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea . J IND MICROBIOL BIOTECHNOL 33, 600–609 (2006). https://doi.org/10.1007/s10295-006-0094-3
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DOI: https://doi.org/10.1007/s10295-006-0094-3