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. 2017 Feb;40(2):201-209. doi: 10.1007/s00449-016-1687-5. Epub 2016 Oct 5.

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.

Keywords: Erythromycin; Methylmalonyl-CoA mutase; N-propanol; Saccharopolyspora erythraea; mutB.

MeSH terms

  • Bacterial Proteins / genetics*
  • Citric Acid Cycle / genetics*
  • Erythromycin / biosynthesis*
  • Gene Knockdown Techniques*
  • Methylmalonyl-CoA Mutase / genetics*
  • Propionates / metabolism*
  • Saccharopolyspora* / genetics
  • Saccharopolyspora* / metabolism

Substances

  • Bacterial Proteins
  • Propionates
  • Erythromycin
  • Methylmalonyl-CoA Mutase
  • propionic acid