Blocking the flow of propionate into TCA cycle through a mutB knockout leads to a significant increase of erythromycin production by an industrial strain of Saccharopolyspora erythraea

Abstract

A high erythromycin producing mutant strain Saccharopolyspora erythraea HL3168 E3-ΔmutB was constructed by deleting mutB (SACE_5639) gene encoding the beta subunit of methylmalonyl-CoA mutase of an industrial strain of S. erythraea HL3168 E3. Industrial media and process control strategies were adopted in a 5 L bioreactor for characterizing the physiological parameters. The total erythromycin titer and erythromycin A concentration in mutant were 46.9 (12740.5 μg/mL) and 64.9 % (8094.4 μg/mL) higher than those in original strain, respectively, which were comparable to industrial erythromycin production. The specific glucose and n-propanol consumption rates were increased by 52.4 and 39.8 %, respectively. During the rapid erythromycin synthesis phase, the yield of erythromycin on n-propanol also increased from 24.3 % in control group to 66.9 % in mutant group. Meanwhile, the specific formation rates of methylmalonyl-CoA and propionyl-CoA, two crucial precursors for erythromycin synthesis, were 1.89- and 2.02-folds higher in the mutant strain, respectively.

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Acknowledgments

This work was financially supported by a Grant from the Major State Basic Research Development Program of China (973 Program, No. 2012CB721006) and National Natural Science Foundation of China (No. 21276081).

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Correspondence to Ju Chu or Mingzhi Huang.

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Chen, C., Hong, M., Chu, J. et al. Blocking the flow of propionate into TCA cycle through a mutB knockout leads to a significant increase of erythromycin production by an industrial strain of Saccharopolyspora erythraea . Bioprocess Biosyst Eng 40, 201–209 (2017). https://doi.org/10.1007/s00449-016-1687-5

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Keywords

  • Saccharopolyspora erythraea
  • Erythromycin
  • N-propanol
  • Methylmalonyl-CoA mutase
  • mutB