Affiliation:
1. National Food Research Institute,1 and
2. Exploratory Research Laboratories, Fujisawa Pharmaceutical Co.,2Tsukuba, Ibaraki, Japan
Abstract
ABSTRACT
Physiological differentiation (including antibiotic production) in microorganisms usually starts when cells encounter adverse environmental conditions and is frequently accompanied by an increase in the accumulation of intracellular ppGpp. We have found that the acquisition of certain streptomycin-resistant (
str
) mutations enables cells to overproduce antibiotics, demonstrating an increase in productivity 5- to 50-fold greater than that of wild-type strains. The frequency of such antibiotic-overproducing strains among the
str
mutants was shown to range from 3 to 46%, as examined with several strains of the genera
Streptomyces
,
Bacillus
, and
Pseudomonas
. Analysis of
str
mutants from
Bacillus subtilis
Marburg 168 revealed that a point mutation occurred within the
rpsL
gene, which encodes the ribosomal protein S12, changing Lys-56 (corresponding to Lys-43 in
Escherichia coli
) to Asn, Arg, Thr, or Gln. Antibiotic productivity increased in a hierarchical manner depending upon which amino acid residue replaced Lys at this position. The
strA1
mutation, a genetic marker frequently used for mapping, had no effect on antibiotic productivity even though it was found to result in an amino acid alteration of Lys-56 to Ile. Gene replacement experiments with the
str
alleles demonstrated unambiguously that the
str
mutation is responsible for the antibiotic overproductivity observed. These results offer a rational approach for improving the production of antibiotic (secondary metabolism) from microorganisms.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference59 articles.
1. Mutations in ribosomal proteins S4 and S12 influence the high order structure of 16S ribosomal RNA.;Allen P. N.;J. Mol. Biol.,1989
2. Studies of pyrrolnitrin, a new antibiotic. I. Isolation and properties of pyrrolnitrin.;Arima K.;J. Antibiot. (Tokyo) Ser. A,1965
3. Cashel
M.
Gentry
D. R.
Hernandez
V. J.
Vinella
D.
The stringent response
Escherichia coli and Salmonella: cellular and molecular biology
2nd ed.
Neidhardt
F. C.
Curtiss
R.
III
Ingraham
J. L.
Lin
E. C. C.
Low
K. B.
Magasanik
B.
Reznikoff
W. S.
Riley
M.
Schaechter
M.
Umbarger
H. E.
1996
1458
1496
ASM Press
Washington D.C
4. The ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2) plays a conditional role in antibiotic production and morphological differentiation
5. Champness
W. C.
Chater
K. F.
Regulation and integration of antibiotic production and morphological differentiation in Streptomyces spp.
Regulation of bacterial differentiation.
Piggot
P.
Moran
C. P.
Youngman
P.
1994
61
93
American Society for Microbiology
Washington D.C
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