Identification and Heterologous Expression of the Chaxamycin Biosynthesis Gene Cluster from Streptomyces leeuwenhoekii

• Jean Franco Castro ^[1] ; Valeria Razmilic ^[1] ; Juan Pablo Gomez-Escribano ^[2] ; Barbara Andrews ^[1] ; Juan A. Asenjo ^[1] ; Mervyn J. Bibb ^[2]
  1. [1] Universidad de Chile

     Universidad de Chile

     Santiago, Chile

     
  2. [2] John Innes Centre

     John Innes Centre

     Norwich District, Reino Unido

     
• Localización: Applied and Environmental Microbiology, ISSN 0099-2240, Vol. 81, Nº 17, 2015, págs. 5820-5831
• Idioma: inglés
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• Resumen

  • 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.