Novel Genes That Influence Development inStreptomyces coelicolor

Abstract

Filamentous soil bacteria of the genus Streptomyces carry out complex developmental cycles that result in sporulation and production of numerous secondary metabolites with pharmaceutically important activities. To further characterize the molecular basis of these developmental events, we screened for mutants of Streptomyces coelicolor that exhibit aberrant morphological differentiation and/or secondary metabolite production. On the basis of this screening analysis and the subsequent complementation analysis of the mutants obtained we assigned developmental roles to a gene involved in methionine biosynthesis (metH) and two previously uncharacterized genes (SCO6938 and SCO2525) and we reidentified two previously described developmental genes (bldA and bldM). In contrast to most previously studied genes involved in development, the genes newly identified in the present study all appear to encode biosynthetic enzymes instead of regulatory proteins. The MetH methionine synthase appears to be required for conversion of aerial hyphae into chains of spores, SCO6938 is a probable acyl coenzyme A dehydrogenase that contributes to the proper timing of aerial mycelium formation and antibiotic production, and SCO2525 is a putative methyltransferase that influences various aspects of colony growth and development.

Targeted disruption of homoserine dehydrogenase gene and its effect on cephamycin C production in Streptomyces clavuligerus

“…Besides the aforementioned growth reduction, AK39 was defective in sporulation on MM supplemented with L-methionine and L-threonine, but not on sporulation agar. This Wnding accorded well with that of Gehring et al [9] who reported that an L-methionine auxotroph of S. coelicolor had developmental defects which also increased secondary metabolite production. A functional metH (methionine synthase gene) was required for conversion of aerial hyphae into chains of spores in this mutant.…”

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

“…It was suggested that the three proteins are involved in transducing an environmental signal that influences developmental progression and that SCO4542 mutants are abnormally rich in a cell type that produces pigmented antibiotics (192). Streptomycetes all have multiple gene clusters comprising paralogues of SCO4542 to -4 (191,193). One such cluster is the abaA cluster, discovered earlier through its presence in a DNA fragment that stimulated S. coelicolor colony pigmentation at high copy number (194).…”

Predicted highly expressed genes in the genomes of Streptomyces coelicolor and Streptomyces avermitilis and the implications for their metabolism

“…Methionine synthase is a vitamin B 12 -dependent enzyme that catalyses the final step in methionine biosynthesis, the conversion of homocysteine to methionine. Recent study showed that the disruption of the metH gene in S. coelicolor not only affected vegetative growth on minimal medium, but on rich medium blocked the conversion of aerial hyphae into chains of spores (Gehring et al, 2004). Glutamine synthetase is responsible for the ATPdependent synthesis of glutamine from ammonium and glutamate.…”