Functional identification of the gene encoding the enzyme involved in mannosylation in ramoplanin biosynthesis in Actinoplanes sp.
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  • 作者:Jun-Sheng Chen (1)
    Yuan-Xi Wang (1)
    Lei Shao (1)
    Hai-Xue Pan (1)
    Ji-An Li (1)
    Hui-Min Lin (1)
    Xiao-Jing Dong (1)
    Dai-Jie Chen (1)
  • 关键词:Glycosyltransferase ; Mannosyltransferase ; Non ; ribosomal peptide synthetase ; Ramoplanin
  • 刊名:Biotechnology Letters
  • 出版年:2013
  • 出版时间:September 2013
  • 年:2013
  • 卷:35
  • 期:9
  • 页码:1501-1508
  • 全文大小:367KB
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  • 作者单位:Jun-Sheng Chen (1)
    Yuan-Xi Wang (1)
    Lei Shao (1)
    Hai-Xue Pan (1)
    Ji-An Li (1)
    Hui-Min Lin (1)
    Xiao-Jing Dong (1)
    Dai-Jie Chen (1)

    1. State Key Lab of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, 1320 West Beijing Road, Shanghai, 200040, China
文摘
Ramoplanin is a lipopeptide antibiotic active against multi-drug-resistant, Gram-positive pathogens. Structurally, it contains a di-mannose moiety attached to the peptide core at Hpg11. The biosynthetic gene cluster of ramoplanin has already been reported and the assembly of the depsipeptide has been elucidated but the mechanism of transferring sugar moiety to the peptide core remains unclear. Sequence analysis of the biosynthetic gene cluster indicated ramo-orf29 was a mannosyltransferase candidate. To investigate the involvement of ramo-orf29 in ramoplanin biosynthesis, gene inactivation and complementation have been conducted in Actinoplanes sp. ATCC 33076 by homologous recombination. Metabolite analysis revealed that the ramo-orf29 inactivated mutant produced no ramoplanin but the ramoplanin aglycone. Thus, ramo-orf29 codes for the mannosyltransferase in the ramoplanin biosynthesis pathway. This lays the foundation for further exploitation of the ramoplanin mannosyltransferase and aglycone in combinatorial biosynthesis.

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