title: Characterization of biosynthetic genes of ascamycin/dealanylascamycin featuring a 5'-O-sulfonamide moiety in Streptomyces sp. JCM9888.
abstract: Ascamycin (ACM) and dealanylascamycin (DACM) are nucleoside antibiotics elaborated by Streptomyces sp. JCM9888. The later shows broad spectrum inhibition activity to various gram-positive and gram-negative bacteria, eukaryotic Trypanosoma and is also toxic to mice, while ascamycin is active against very limited microorganisms, such as Xanthomonas. Both compounds share an unusual 5'-O-sulfonamide moiety which is attached to an adenosine nucleoside. In this paper, we first report on the 30 kb gene cluster (23 genes, acmA to acmW) involved in the biosynthesis of these two antibiotics and a biosynthetic assembly line was proposed. Of them, six genes (AcmABGKIW) are hypothetical genes involved in 5'-O-sulfonamide formation. Two flavin adenine dinucleotide (FAD)-dependent chlorinase genes acmX and acmY were characterized which are significantly remote from acmA-W and postulated to be required for adenine C2-halogenation. Notably gene disruption of acmE resulted in a mutant which could only produce dealanylascamycin but was blocked in its ability to biosynthesize ascamycin, revealing its key role of conversion of dealanylascamycin to ascamycin.
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education) and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, 430071, PR China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education) and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, 430071, PR China.
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Qi
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education) and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, 430071, PR China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Tao
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education) and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, 430071, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education) and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, 430071, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Jason
authors.initials: J
authors.lastname: Chan
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education) and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, 430071, PR China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
mesh_terms: D015762:2-Chloroadenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism
chemical_list: D013449:Sulfonamides; D015762:2-Chloroadenosine; C035935:5'-sulfamoyl-2-chloroadenosine; C042369:ascamycin; D000241:Adenosine