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Development of a Biosensor Concept to Detect the Production of Cluster-Specific Secondary Metabolites.
Sun, Yi-Qian Busche, Tobias Rückert, Christian Paulus, Constanze Rebets, Yuriy Novakova, Renata Kalinowski, Jörn Kormanec, Jan Sekurova, Olga N
Sun, Yi-Qian
Busche, Tobias
Rückert, Christian
Paulus, Constanze
Rebets, Yuriy
Novakova, Renata
Kalinowski, Jörn
Kormanec, Jan
Sekurova, Olga N
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2017-06-16
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Abstract
Genome mining of actinomycete bacteria aims at the discovery of novel bioactive secondary metabolites that can be developed into drugs. A new repressor-based biosensor to detect activated secondary metabolite biosynthesis gene clusters in Streptomyces was developed. Biosynthetic gene clusters for undecylprodigiosin and coelimycin in the genome of Streptomyces lividans TK24, which encoded TetR-like repressors and appeared to be almost “silent” based on the RNA-seq data, were chosen for the proof-of-principle studies. The bpsA reporter gene for indigoidine synthetase was placed under control of the promotor/operator regions presumed to be controlled by the cluster-associated TetR-like repressors. While the biosensor for undecylprodigiosin turned out to be nonfunctional, the coelimycin biosensor was shown to perform as expected, turning on biosynthesis of indigoidine in response to the concomitant production of coelimycin. The developed reporter system concept can be applied to those cryptic gene clusters that encode metabolite-sensing repressors to speed up discovery of novel bioactive compounds in Streptomyces.
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ACS Synth Biol. 2017 Jun 16;6(6):1026-1033. doi: 10.1021/acssynbio.6b00353. Epub 2017 Mar 3.
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2161-5063
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Attribution-NonCommercial-ShareAlike 4.0 International