Synthetic Biology
Synthetic biology of antibiotic production
Eriko Takano
University of Groningen, the Netherlands
Research interests
Synthetic biology of antibiotic production
Novel antibiotic discovery by post genomics
Gamma butyrolactone signalling system in Streptomyces coelicolor
Noncoding RNA in Streptomyces
Metabolomic analysis in Streptomyces
Metabolite modelling and bioinformatics
Email
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University of Groningen
Speaker abstract
Streptomyces bacteria are well known for their ability to produce an immense diversity of secondary metabolites, including many antibiotics. The underlying biosynthetic machinery is a particularly interesting target for synthetic biology, due to its inherent modularity at multiple levels1,2. A treasure trove of antibiotic biosynthesis gene clusters has been identified by genome sequencing, typically 20–50 per genome3,4. We can use synthetic biology to re-engineer the bacterial genomes to awaken this multitude of cryptic antibiotic clusters. We have already demonstrated the potential of this strategy by awakening the cryptic/orphan CPK gene cluster5, which produces a novel antibacterial compound. Generalizing this approach using standardized molecular modules will become a central tool for discovering new bioactive compounds, ranging from anti-cancer drugs to antibiotics6.
References
1. Medema MH, Breitling R, Bovenberg RAL, Takano E. 2011. Exploiting Plug-and-Play Synthetic Biology for Drug Discovery and Production in Microbes. Nature Rev Microbiol 9: 131–137.
2. Medema MH, van Raaphorst R, Takano E, Breitling R. 2012. Computational tools for the synthetic design of biochemical pathways. Nature Rev Microbiol 10: 191-202.
3. Medema MH, Trefzer A, Kovalchuk A, van den Berg M, Müller U, Heijne W, Wu L, Alam MT, Ronning CM, Nierman WC, Bovenberg RAL, Breitling R, Takano E. 2010. The sequence of a 1.8-Mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways. Genome Biology and Evolution 2: 212–224.
4. Medema MH, Balin K, Cimermanic P, de Jager V, Zakrzewski P, Fischbach MA, Weber T, Takano E, Breitling R. 2011. antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucl Acids Res 39: W339–W346.
5. Gottelt M, Gomez-Escribano JP, Bibb M, Takano E. 2010. Awakening cryptic antibiotic gene clusters: The CPK gene cluster in Streptomyces coelicolor is involved in the production of a yellow pigmented secondary metabolite. Microbiology 156: 2343–2353.
6. Medema MH, Alam MT, Breitling R, Takano E. 2011. The future of industrial antibiotic production: from random mutagenesis to synthetic biology. Bioengineered Bugs 2: 4.
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