title: Identification of a Novel Lincomycin Resistance Mutation Associated with Activation of Antibiotic Production in Streptomyces coelicolor A3(2).
abstract: Comparative genome sequencing analysis of a lincomycin-resistant strain of Streptomyces coelicolor A3(2) and the wild-type strain identified a novel mutation conferring a high level of lincomycin resistance. Surprisingly, the new mutation was an in-frame DNA deletion in the genes SCO4597 and SCO4598, resulting in formation of the hybrid gene linR. SCO4597 and SCO4598 encode two histidine kinases, which together with SCO4596, encoding a response regulator, constitute a unique two-component system. Sequence analysis indicated that these three genes and their arrangement patterns are ubiquitous among all Streptomyces genomes sequenced to date, suggesting these genes play important regulatory roles. Gene replacement showed that this mutation was responsible for the high level of lincomycin resistance, the overproduction of the antibiotic actinorhodin, and the enhanced morphological differentiation of this strain. Moreover, heterologous expression of the hybrid gene linR in Escherichia coli conferred resistance to lincomycin in this organism. Introduction of the hybrid gene linR in various Streptomyces strains by gene engineering technology may widely activate and/or enhance antibiotic production.
authors.affiliation: Harbor Branch Oceanographic Institute, Florida Atlantic University, Fort Pierce, Florida, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Izawa
authors.affiliation: Harbor Branch Oceanographic Institute, Florida Atlantic University, Fort Pierce, Florida, USA.|College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.
authors.forename: Xiaoge
authors.initials: X
authors.lastname: Yang
authors.affiliation: Harbor Branch Oceanographic Institute, Florida Atlantic University, Fort Pierce, Florida, USA.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Life Sciences, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Life Sciences, Hiroshima Institute of Technology, Hiroshima, Japan k.ochi.bz@it-hiroshima.ac.jp.
authors.forename: Kozo
authors.initials: K
authors.lastname: Ochi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D008034:Lincomycin / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D048372:Streptomyces coelicolor / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D008034:Lincomycin
keywords: Streptomyces coelicolor; Streptomyces lividans; antibiotic production; cryptic genes; lincomycin resistance; two-component system