A single amino acid substitution in region 1.2 of the principal a factor of Streptomyces coelicolor A3(2) results in pleiotropic loss of antibiotic production
B. Aigle et al., A single amino acid substitution in region 1.2 of the principal a factor of Streptomyces coelicolor A3(2) results in pleiotropic loss of antibiotic production, MOL MICROB, 37(5), 2000, pp. 995-1004
Antibiotic production in streptomycetes generally occurs in a growth phase-
dependent and developmentally co-ordinated manner, and is subject to pathwa
y-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 ga
mma-butyrolactone, SCB1, that can elicit precocious Act and Red production.
Clones encoding the principal and essential a factor (sigma(HrdB)) Of S. c
oelicolor restored Act and Red production in the afsB mutant BH5. A highly
conserved glycine (G) at position 243 of sigma(HrdB) was shown to be replac
ed by aspartate (D) in BH5. Replacement of G243 by D in the afsB(+) strain
M145 reproduced the afsB phenotype. The antibiotic deficiency correlated wi
th reduced transcription of acfII-ORF4 and redo, pathway-specific regulator
y 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 SC
B1 synthesis. The G-243D substitution, which lies in the highly conserved 1
.2 region of undefined function, had no effect on growth rate or morphologi
cal differentiation, and appears specifically to affect antibiotic producti
on.