GLOBAL NEGATIVE REGULATION OF STREPTOMYCES-COELICOLOR ANTIBIOTIC-SYNTHESIS MEDIATED BY AN ABSA-ENCODED PUTATIVE SIGNAL-TRANSDUCTION SYSTEM

Streptomycete antibiotic synthesis is coupled to morphological differe ntiation such that antibiotics are produced as a colony sporulates. St reptomyces coelicolor produces several structurally and genetically di stinct antibiotics. The S. coelicolor absA locus was defined by four U V-induced mutations that globally blocked antibiotic biosynthesis with out blocking morphological differentiation. We show that the absA locu s encodes a putative eubacterial two-component sensor kinase-response regulator system. All four mutations lie within a single open reading frame, designated absA1, which is predicted to encode a sensor histidi ne kinase. A second gene downstream of absA1, absA2, is predicted to e ncode the cognate response regulator. In marked contrast to the antibi otic-deficient phenotype of the previously described absA mutants, the phenotype caused by disruption mutations in the absA locus is precoci ous hyperproduction of the antibiotics actinorhodin and undecylprodigi osin. Precocious hyperproduction of these antibiotics is correlated wi th premature expression of XylE activity in a transcriptional fusion t o an actinorhodin biosynthetic gene. We propose that the absA locus en codes a Signal transduction mechanism that negatively regulates synthe sis of the multiple antibiotics produced by S. coelicolor.