Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays

被引:158
作者
Huang, JQ [1 ]
Lih, CJ [1 ]
Pan, KH [1 ]
Cohen, SN [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
关键词
microarray; antibiotic; pathway; cluster; regulation; transcription;
D O I
10.1101/gad.943401
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The eubacterial species Streptomyces coelicolor proceeds through a complex growth cycle in which morphological differentiation/development is associated with a transition from primary to secondary metabolism and the production of antibiotics. We used DNA microarrays and mutational analysis to investigate the expression of individual genes and multigene antibiotic biosynthetic pathways during these events. We identified expression patterns in biosynthetic, regulatory, and ribosomal protein genes that were associated highly specifically with particular stages of development. A knowledge-based algorithm that correlates temporal changes in expression with chromosomal position identified groups of contiguous genes expressed at discrete stages of morphological development, inferred the boundaries of known antibiotic synthesis gene loci, and revealed novel physical clusters of coordinately regulated genes. Microarray analysis of RNA from cells mutated in genes regulating synthesis of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) identified proximate and distant sites that contain putative ABC transporter and two-component system genes expressed coordinately with genes of specific biosynthetic pathways and indicated the existence of two functionally and physically discrete regulons in the Red pathway.
引用
收藏
页码:3183 / 3192
页数:10
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