Dramatic activation of antibiotic production in Streptomyces coelicolor by cumulative drug resistance mutations.

Abstract:

:We recently described a new method to activate antibiotic production in bacteria by introducing a mutation conferring resistance to a drug such as streptomycin, rifampin, paromomycin, or gentamicin. This method, however, enhanced antibiotic production by only up to an order of magnitude. Working with Streptomyces coelicolor A3(2), we established a method for the dramatic activation of antibiotic production by the sequential introduction of multiple drug resistance mutations. Septuple and octuple mutants, C7 and C8, thus obtained by screening for resistance to seven or eight drugs, produced huge amounts (1.63 g/liter) of the polyketide antibiotic actinorhodin, 180-fold higher than the level produced by the wild type. This dramatic overproduction was due to the acquisition of mutant ribosomes, with aberrant protein and ppGpp synthesis activity, as demonstrated by in vitro protein synthesis assays and by the abolition of antibiotic overproduction with relA disruption. This new approach, called "ribosome engineering," requires less time, cost, and labor than other methods and may be widely utilized for bacterial strain improvement.

journal_name

Appl Environ Microbiol

authors

Wang G,Hosaka T,Ochi K

doi

10.1128/AEM.02800-07

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

2834-40

issue

9

eissn

0099-2240

issn

1098-5336

pii

AEM.02800-07

journal_volume

74

pub_type

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