biostudies-literatureUnknown97(1)Ochi KGenome 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.Applied microbiology and biotechnology87-98https://www.ebi.ac.uk/biostudies/studies/S-EPMC3536979biostudies-literatureNew strategies for drug discovery: activation of silent or weakly expressed microbial gene clusters.PMC3536979Hosaka TOchi KfalseNew strategies for drug discovery: activation of silent or weakly expressed microbial gene clusters.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.2013-01-01T00:00:00Z2013 Jan2021-03-18T08:45:44Z2019-03-27T01:02:38ZS-EPMC35369792314353510.1007/s00253-012-4551-9