title: Characterization of the biosynthesis gene cluster for the pyrrole polyether antibiotic calcimycin (A23187) in Streptomyces chartreusis NRRL 3882.
abstract: The pyrrole polyether antibiotic calcimycin (A23187) is a rare ionophore that is specific for divalent cations. It is widely used as a biochemical and pharmacological tool because of its multiple, unique biological effects. Here we report on the cloning, sequencing, and mutational analysis of the 64-kb biosynthetic gene cluster from Streptomyces chartreusis NRRL 3882. Gene replacements confirmed the identity of the gene cluster, and in silico analysis of the DNA sequence revealed 27 potential genes, including 3 genes for the biosynthesis of the α-ketopyrrole moiety, 5 genes that encode modular type I polyketide synthases for the biosynthesis of the spiroketal ring, 4 genes for the biosynthesis of 3-hydroxyanthranilic acid, an N-methyltransferase tailoring gene, a resistance gene, a type II thioesterase gene, 3 regulatory genes, 4 genes with other functions, and 5 genes of unknown function. We propose a pathway for the biosynthesis of calcimycin and assign the genes to the biosynthesis steps. Our findings set the stage for producing much desired calcimycin derivatives using genetic modification instead of chemical synthesis.
authors.affiliation: Laboratory of Microbial Metabolism, School of Life Science & Biotechnology, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Qiulin
authors.initials: Q
authors.lastname: Wu
authors.forename: Jingdan
authors.initials: J
authors.lastname: Liang
authors.forename: Shuangjun
authors.initials: S
authors.lastname: Lin
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhou
authors.forename: Linquan
authors.initials: L
authors.lastname: Bai
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000001:Calcimycin / Q000096:biosynthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000001:Calcimycin