title: Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii.
abstract: Streptomyces leeuwenhoekii, isolated from the hyperarid Atacama Desert, produces the new ansamycin-like compounds chaxamycins A to D, which possess potent antibacterial activity and moderate antiproliferative activity. We report the development of genetic tools to manipulate S. leeuwenhoekii and the identification and partial characterization of the 80.2-kb chaxamycin biosynthesis gene cluster, which was achieved by both mutational analysis in the natural producer and heterologous expression in Streptomyces coelicolor A3(2) strain M1152. Restoration of chaxamycin production in a nonproducing ΔcxmK mutant (cxmK encodes 3-amino-5-hydroxybenzoic acid [AHBA] synthase) was achieved by supplementing the growth medium with AHBA, suggesting that mutasynthesis may be a viable approach for the generation of novel chaxamycin derivatives.
authors.affiliation: Centre for Biotechnology and Bioengineering, Department of Chemical Engineering and Biotechnology, Universidad de Chile, Santiago, Chile Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Jean Franco
authors.initials: JF
authors.lastname: Castro
authors.affiliation: Centre for Biotechnology and Bioengineering, Department of Chemical Engineering and Biotechnology, Universidad de Chile, Santiago, Chile Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Valeria
authors.initials: V
authors.lastname: Razmilic
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Gomez-Escribano
authors.affiliation: Centre for Biotechnology and Bioengineering, Department of Chemical Engineering and Biotechnology, Universidad de Chile, Santiago, Chile.
authors.forename: Barbara
authors.initials: B
authors.lastname: Andrews
authors.affiliation: Centre for Biotechnology and Bioengineering, Department of Chemical Engineering and Biotechnology, Universidad de Chile, Santiago, Chile.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Asenjo
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, United Kingdom mervyn.bibb@jic.ac.uk.
authors.forename: Mervyn J
authors.initials: MJ
authors.lastname: Bibb
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D053898:Biosynthetic Pathways; D005810:Multigene Family; D012294:Rifamycins / Q000096:biosynthesis* / Q000737:chemistry; D013302:Streptomyces / Q000235:genetics*; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012294:Rifamycins; C581434:chaxamycin A; C581435:chaxamycin D