title: 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.
authors.affiliation: 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.
authors.forename: Chongchong
authors.initials: C
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ming
authors.initials: M
authors.lastname: Hong
authors.affiliation: 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. juchu@ecust.edu.cn.
authors.forename: Ju
authors.initials: J
authors.lastname: Chu
authors.affiliation: 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. huangmz@ecust.edu.cn.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Liming
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: 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.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Yingping
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D002952:Citric Acid Cycle / Q000235:genetics*; D004917:Erythromycin / Q000096:biosynthesis*; D055785:Gene Knockdown Techniques; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics*; D011422:Propionates / Q000378:metabolism*; D016930:Saccharopolyspora / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011422:Propionates; D004917:Erythromycin; D008765:Methylmalonyl-CoA Mutase; C029658:propionic acid
keywords: Erythromycin; Methylmalonyl-CoA mutase; N-propanol; Saccharopolyspora erythraea; mutB