Regulation of branched-chain amino acid catabolism: glucose limitation enhances the component of isovalerylspiramycin for the bitespiramycin production.
4''-O-isovalerylspiramycins are the major components of bitespiramycin complex consisting of a group of 4''-O-acylated spiramycins. The availability of isovaleryl group, usually in vivo derived from leucine, one of the branched-chain amino acids, affects the content of isovaleryispiramycin significantly. In this study, the effect of glucose on the activity of branched-chain alpha-keto acid dehydrogenase (BCKDH), which catalyzed the rate-limiting as well as the first irreversible reaction oxidative decarboxylation for branched-chain amino acids degradation, and isovaleryispiramycin biosynthesis was investigated. In the initial glucose concentration experiment, when the residual glucose concentration in the medium declined to 2-4 g/L, the BCKDH activity rose rapidly, and glucose deprivation and the summit of BCKDH activity appeared nearly at the same time. After a delay of about 6 h, the maximal isovalerylspiramycin content was observed. However, the shortage of glucose at the later production phase resulted in the marked decrease in BCKDH activity and isovaleryispiramycin content. In the fermentation in a 50 L fermentor, glucose feeding at the late production phase helped to maintain the residual glucose concentration between 0 and 1 g/L, leading to the high level of BCKDH activity and thus isovalerylspiramycin content. These suggested that glucose concentration could be used as a key parameter to regulate BCKDH activity and isovaleryispiramycin biosynthesis in the bitespiramycin production.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. yhwang@ecust.edu.cn
Yong-Hong
YH
Wang
Chun-Hai
CH
Wu
Ju
J
Chu
Yu-You
YY
Hao
Ying-Ping
YP
Zhuang
Si-Liang
SL
Zhang
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000737:chemistry; D000597:Amino Acids, Branched-Chain / Q000737:chemistry*; D001709:Biotechnology / Q000379:methods*; D002384:Catalysis; D003470:Culture Media / Q000378:metabolism; D005285:Fermentation; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000737:chemistry*; D007218:Industrial Microbiology / Q000379:methods*; D007930:Leucine / Q000737:chemistry; D008660:Metabolism; D008956:Models, Chemical; D015572:Spiramycin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D013997:Time Factors
D000597:Amino Acids, Branched-Chain; D003470:Culture Media; C503764:bitespiramycin; D015572:Spiramycin; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D007930:Leucine; D005947:Glucose; C423662:carrimycin