title: Leucine improves the component of isovalerylspiramycins for the production of bitespiramycin.
abstract: Bitespiramycin, a group of 4''-O-acylated spiramycins with 4''-O-isovalerylspiramycins as the major components, is produced by recombinant spiramycin-producing strain Streptomyces spiramyceticus harboring a 4''-O-acyltransferase gene from a carbomycin-producing strain S. mycarofaciens 1748. The effects of leucine feeding on the bitespiramycin fermentation, especially the synthesis of isovalerylspiramycin components, were investigated. The experiment was initially performed in flask culture under the condition of feeding 15.4 mmol/l of leucine at 72 h fermentation, and the culture without leucine feeding was used as control. When 15.4 mmol/l leucine was fed at 72 h, 51.3 +/- 0.33% total isovalerylspiramycins was recorded compared to 40.9 +/- 0.26% under the control condition after 96 h of fermentation. The improvement of total isovalerylspiramycin content was further achieved in 15 l fermentation when 15.4 mmol/l of leucine was supplemented from 65 to 72 h. These results indicated that isovaleryl group derived from leucine catabolism could act as the precursor of the 4'' side chain of bitespiramycin, which profoundly enhanced the synthesis of isovalerylspiramycins in the bitespiramycin complex.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 200237, Shanghai, People's Republic of China. zhenlin1975@126.com
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Li
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Ju
authors.initials: J
authors.lastname: Chu
authors.forename: Ying-Ping
authors.initials: YP
authors.lastname: Zhuang
authors.forename: Si-Liang
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D004305:Dose-Response Relationship, Drug; D007930:Leucine / Q000494:pharmacology*; D008660:Metabolism; D015572:Spiramycin / Q000031:analogs & derivatives* / Q000378:metabolism; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism*
chemical_list: C503764:bitespiramycin; D015572:Spiramycin; D007930:Leucine