Genetic characterization of the chlorothricin gene cluster as a model for spirotetronate antibiotic biosynthesis.
The biosynthetic gene cluster for chlorothricin (CHL) was localized to a 122 kb contiguous DNA from Streptomyces antibioticus DSM 40725, and its involvement in CHL biosynthesis was confirmed by gene inactivation and complementation. Bioinformatic analysis of the sequenced 111.989 kb DNA region revealed 42 open reading frames, 35 of which were defined to constitute the CHL gene cluster. An assembly model for CHL biosynthesis from D-olivose, 2-methoxy-5-chloro-6-methylsalicyclic acid, and chlorothricolide building blocks was proposed. This work represents cloning of a gene cluster for spirotetronate antibiotic biosynthesis and sets the stage to investigate the unusual macrolide biosynthesis including tandem Diels-Alder cyclizations, Baeyer-Villiger oxidation, and incorporation of an enoylpyruvate unit.
Jia
Xin-Ying
XY
State Key Laboratory of Bioorganic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai, 200032, China.
Tian
Zhen-Hua
ZH
Shao
Lei
L
Qu
Xu-Dong
XD
Zhao
Qun-Fei
QF
Tang
Jian
J
Tang
Gong-Li
GL
Liu
Wen
W
D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D050260:Carbohydrate Metabolism; D002713:Chlorine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D017124:Conserved Sequence; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics*; D010084:Oxidation-Reduction; D012459:Salicylates / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013303:Streptomyces antibioticus / Q000235:genetics / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012459:Salicylates; D002713:Chlorine; C000451:chlorothricin; C005236:6-methylsalicylic acid