title: Activating a Cryptic Ansamycin Biosynthetic Gene Cluster To Produce Three New Naphthalenic Octaketide Ansamycins with n-Pentyl and n-Butyl Side Chains.
abstract: Genome mining is a rational approach to discovering new natural products. The genome sequence analysis of Streptomyces sp. LZ35 revealed the presence of a putative ansamycin gene cluster (nam). Constitutive overexpression of the pathway-specific transcriptional regulatory gene nam1 successfully activated the nam gene cluster, and three novel naphthalenic octaketide ansamycins were discovered with unprecedented n-pentylmalonyl-CoA or n-butylmalonyl-CoA extender units. This study represents the first example of discovering novel ansamycin scaffolds via activation of a cryptic gene cluster.
authors.affiliation: †Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, P. R. China.
authors.forename: Shanren
authors.initials: S
authors.lastname: Li
authors.affiliation: †Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, P. R. China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Li
authors.affiliation: †Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, P. R. China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Lu
authors.affiliation: †Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, P. R. China.
authors.forename: Juanli
authors.initials: J
authors.lastname: Zhang
authors.affiliation: ‡State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: ‡State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, P. R. China.
authors.forename: Haoxin
authors.initials: H
authors.lastname: Wang
authors.affiliation: †Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, P. R. China.|‡State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, P. R. China.
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D005810:Multigene Family; D017828:Rifabutin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013302:Streptomyces / Q000235:genetics*
chemical_list: D001688:Biological Products; D017828:Rifabutin