title: Identification of JadG as the B ring opening oxygenase catalyzing the oxidative C-C bond cleavage reaction in jadomycin biosynthesis.
abstract: Jadomycin B is a member of atypical angucycline antibiotics whose biosynthesis involves a unique ring opening C-C bond cleavage reaction. Here, we firmly identified JadG as the enzyme responsible for the B ring opening reaction in jadomycin biosynthesis. In vitro analysis of the JadG catalyzed reaction revealed that it requires FMNH(2) or FADH(2) as cofactors in the conversion of dehydrorabelomycin to jadomycin A. The cofactors could be supplied by either a cluster-situated flavin reductase JadY or the Escherichia coli Fre. JadY was characterized as a NAD(P)H-dependent FMN/FAD reductase, with FMN as the preferred substrate. Disruption mutant of jadY still produced jadomycin, indicating that the function of JadY could be substituted by other enzymes in the host. JadG represents the biochemically verified member of an enzyme class catalyzing an unprecedented C-C bond cleavage reaction.
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Fan
authors.forename: Guohui
authors.initials: G
authors.lastname: Pan
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Peng
authors.forename: Jianting
authors.initials: J
authors.lastname: Zheng
authors.forename: Wubin
authors.initials: W
authors.lastname: Gao
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Weishan
authors.initials: W
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Keqian
authors.initials: K
authors.lastname: Yang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D038181:FMN Reductase / Q000378:metabolism*; D005486:Flavin Mononucleotide / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000031:analogs & derivatives / Q000378:metabolism; D006873:Hydroquinones / Q000378:metabolism; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D009285:Naphthoquinones / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006873:Hydroquinones; D007546:Isoquinolines; D009285:Naphthoquinones; C540087:flavin mononucleotide hydroquinone; C506597:jadomycin A; D005182:Flavin-Adenine Dinucleotide; C081750:jadomycin B; C058805:1,5-dihydro-FAD; D005486:Flavin Mononucleotide; D038181:FMN Reductase; C540768:Fre protein, E coli