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Appl Microbiol Biotechnol. 2013 Jan;97(1):87-98. doi: 10.1007/s00253-012-4551-9. Epub 2012 Nov 11.

New strategies for drug discovery: activation of silent or weakly expressed microbial gene clusters.

Author information

1
Department of Life Science, Hiroshima Institute of Technology, Miyake 2-1-1, Saeki-ku, Hiroshima, 731-5193, Japan. k.ochi.bz@it-hiroshima.ac.jp

Abstract

Genome sequencing of Streptomyces, myxobacteria, and fungi showed that although each strain contains genes that encode the enzymes to synthesize a plethora of potential secondary metabolites, only a fraction are expressed during fermentation. Interest has therefore grown in the activation of these cryptic pathways. We review current progress on this topic, describing concepts for activating silent genes, utilization of "natural" mutant-type RNA polymerases and rare earth elements, and the applicability of ribosome engineering to myxobacteria and fungi, the microbial groups known as excellent searching sources, as well as actinomycetes, for secondary metabolites.

PMID:
23143535
PMCID:
PMC3536979
DOI:
10.1007/s00253-012-4551-9
[Indexed for MEDLINE]
Free PMC Article

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