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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

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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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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, P.O.box 329, Shanghai, 200237, People’s Republic of China

    Chongchong Chen, Ming Hong, Ju Chu, Mingzhi Huang, Liming Ouyang, Xiwei Tian & Yingping Zhuang

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  1. Chongchong Chen
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  2. Ming Hong
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  3. Ju Chu
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  4. Mingzhi Huang
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  5. Liming Ouyang
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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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