Transcriptional regulation of the macs1-fadd1 operon encoding two acyl-coenzyme a synthetases involved in the physiological differentiation of Streptomyces coelicolor

ARABOLAZA ANA, CLAUDIA BANCHIO AND HUGO GRAMAJO

MICROBIOLOGY-UK

Society for General Microbiology

Lugar: Cambridge; Año: 2006 vol. 152 p. 1427 - 1439

1350-0872

The long-chain acyl-CoA synthase FadD1 plays an important role in timing the levels of antibiotic production in Streptomyces coelicolor. FadD1 and macs1, a putative medium-chain acyl-CoA synthase, are part of a two-gene operon, whose expression is induced during stationary phase of growth. Here we report that transcription of the macs1-fadD1 operon is positively regulated by AcsR, a LuxR-type transcriptional regulator. In an acsR mutant, expression of the macs1-fadD1 genes loses its normal up-regulation and the mutant becomes deficient in antibiotic production, in a clear correlation with the phenotype shown by a fadD1 null mutant. The absence of macs1-fadD1 induction in the acsR mutant was restored by complementation with a wild type copy of the acsR gene, showing a strict link between AcsR and induction of the macs1-fadD1 operon. Gel mobility shift assays and DNase I footprinting, indicated that AcsR binds to specific sequences about +162 nucleotides downstream of the macs1 transcriptional start site. In the putative operator sequence we identified three almost identical direct tandem repeats of seven nucleotides where the central sequence is essential for AcsR recognition and binding. Transcriptional fusions of the divergent pacsR and pmacs1 promoters, indicated that AcsR does not regulate its own transcription and that it binds to the operator region to control exclusively the growth phase-induction of the macs1-fadD1 operon.