title: Glycine origin of the methyl substituent on C7'-N of octodiose for the biosynthesis of apramycin.
abstract: Apramycin is unique in the aminoglycoside family due to its octodiose moiety. However, either the biosynthesis process or the precursors involved are largely unknown. Addition of glycine, as well as serine or threonine, to the Streptomyces tenebrabrius UD2 fermentation medium substantially increases the production of apramycin with little effect on the growth of mycelia, indicating that glycine and/or serine might be involved in the biosynthesis of apramycin. The 13C-NMR analysis of [2-13C] glycine-fed (25% enrichment) apramycin showed that glycine specifically and efficiently incorporated into the only N-CH3 substituent of apramycin on the C7' of the octodiose moiety. We noticed that the in vivo concentration of S-adenosyl methionine increased in parallel with the addition of glycine, while the addition of methione in the fermentation medium significantly decreased the productivity of apramycin. Therefore, the methyl donor function of glycine is proposed to be involved in the methionine cycle but methionine itself was proposed to inhibit the methylation and methyl transfer processes a previously reported for the case of rapamycin. The 15N NMR spectra of [2-13C,15N]serine labeled apramycin indicated that serine may also act as a limiting precursor contributing to the -NH2 substituents of apramycin.
authors.affiliation: Laboratory of Molecular Microbiology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Xu
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yinming
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Jin
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Wu
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Li
authors.forename: Yunliu
authors.initials: Y
authors.lastname: Yang
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Jiao
authors.forename: Weihong
authors.initials: W
authors.lastname: Jiang
authors.forename: Houming
authors.initials: H
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Bai
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
mesh_terms: D002240:Carbohydrate Sequence; D002244:Carbon / Q000737:chemistry / Q000378:metabolism; D002247:Carbon Isotopes; D003470:Culture Media; D005998:Glycine / Q000378:metabolism*; D008969:Molecular Sequence Data; D009328:Nebramycin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry / Q000378:metabolism; D016930:Saccharopolyspora / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D003470:Culture Media; D009328:Nebramycin; D013912:Threonine; C011666:apramycin; D012694:Serine; D002244:Carbon; D009584:Nitrogen; D005998:Glycine