A single amino acid substitution in region 1.2 of the principal sigma factor of Streptomyces coelicolor A3(2) results in pleiotropic loss of antibiotic production.

Antibiotic production in streptomycetes generally occurs in a growth phase-dependent and developmentally co-ordinated manner, and is subject to pathway-specific and pleiotropic control. Streptomyces coelicolor A3(2) produces at least four chemically distinct antibiotics, including actinorhodin (Act) and undecylprodigiosin (Red). afsB mutants of S. coelicolor are deficient in the production of both compounds and in the synthesis of a diffusible gamma-butyrolactone, SCB1, that can elicit precocious Act and Red production. Clones encoding the principal and essential sigma factor (sigmaHrdB) of S. coelicolor restored Act and Red production in the afsB mutant BH5. A highly conserved glycine (G) at position 243 of sigmaHrdB was shown to be replaced by aspartate (D) in BH5. Replacement of G243 by D in the afsB+ strain M145 reproduced the afsB phenotype. The antibiotic deficiency correlated with reduced transcription of actII-ORF4 and redD, pathway-specific regulatory genes for Act and Red production respectively. Exogenous addition of SCB1 to the G-243D mutants failed to restore Act and Red synthesis, indicating that loss of antibiotic production was not a result of the deficiency in SCB1 synthesis. The G-243D substitution, which lies in the highly conserved 1.2 region of undefined function, had no effect on growth rate or morphological differentiation, and appears specifically to affect antibiotic production.