Unraveling antibiotic production
- Wim D'Haeze
© BioMed Central Ltd 2002
Received: 8 January 2002
Published: 28 February 2002
Large-scale microarray analyses have provided insights into the genetic control of antibiotic production by Streptomyces coelicolor
Significance and context
The Gram-positive eubacterium Streptomyces coelicolor A3(2) is considered a model soil bacterium, with a complex life cycle involving mycelium growth and spore formation. An interesting feature of S. coelicolor is its capacity to produce useful pharmaceuticals - anti-tumor agents, immunosuppressants and a variety of antibiotics, including the tripyrrole undecylprodigiosin (Red), calcium-dependent lipopeptide (CDA) and the polyketide actinorhodin (Act). These compounds are usually produced during the morphological transition that initiates spore formation. Genes involved in antibiotic synthesis are mostly clustered on the S. coelicolor genome, and antibiotic synthesis involves a reasonably large number of genes, the expression of which is controlled by complex regulatory mechanisms. The availability of the S. coelicolor A3(2) genome sequence and a set of mutants enabled Huang et al. to carry out a global DNA-microarray-based analysis of gene expression during growth and antibiotic synthesis.
Supplementary data to Genes and Development 15:3183-3192 is freely available. Recent information about the entire 8.67 Mb genome sequence of S. coelicolor A3(2), as well as more general information about this soil bacterium, can be consulted at the The Sanger Institute: S. Coelicolor genome project website.
The existence of the entire genome sequence and the ability to carry out global DNA microarray analyses enabled study of the expression of functionally related genes present within loci known to be involved in antibiotic synthesis in S. coelicolor, as well as the discovery of new genes that are distantly located but show coordinated expression.
This study is a major contribution to our understanding of the gene regulation required for antibiotic synthesis in S. coelicolor A3(2) and its results could only have been obtained by a global gene-expression analysis. A major discovery are the sets of genes whose expression is coordinated with that of genes known to be involved in Red or Act synthesis. This hints at possible involvement of these new genes in the synthesis of Red or Act, or of other compounds whose production might be controlled by similar mechanism(s). To pinpoint their precise biological role(s) and to find possible applications, construction of mutants will be required to perform further basic molecular genetic studies.