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Strategies for the Design and Discovery of Novel Antibiotics using Genetic Engineering and Genome Mining

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Antimicrobial Compounds

Abstract

Most bioactive natural products currently known are synthesized by members of the Actinomycetales order. The development of genetic engineering provides novel genetic tools for the modification of known antibiotics and other bioactive compounds to generate derivatives with improved therapeutic properties. This new technology, named combinatorial biosynthesis, is able of introducing structural modifications in bioactive compounds not easily accessible by chemical means. Furthermore, progress in genome sequencing in this group of microorganisms shows that actinomycetes have a greater potential of synthesizing bioactive compounds than was anticipated. Each genome sequenced shows the presence of 18–37 gene clusters potentially directing the biosynthesis of bioactive compounds that have not been previously identified. Novel strategies are being developed to activate these cryptic or silent gene clusters in these microorganisms, allowing the identification of novel potentially bioactive compounds. This chapter will revise the state of the art in this field of research.

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Acknowledgments

Research at the authors’ laboratory has been supported by grants from Spanish Ministry of Science and Innovation (BIO2008-00269 to C. Méndez; BIO2009-07643 to J. A. Salas), Red Temática de Investigación Cooperativa de Centros de Cáncer (Ministry of Health, ISCIII-RETIC RD06/0020/0026) to J. A. Salas, and Obra Social Cajastur to C. Olano.

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  1. Departamento de Biología Funcional and Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006, Oviedo, Spain

    Carlos Olano, Carmen Méndez & José A. Salas

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  1. Carlos Olano
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  2. Carmen Méndez
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  3. José A. Salas
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Correspondence to José A. Salas .

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  1. Faculty of Pharmacy, Dep Microbiology Parasitology, University of Santiago de Compostela, Santiago de Compostela, Spain

    Tomás G. Villa

  2. Biomedical Center, Lund University, Lund, Sweden

    Patricia Veiga-Crespo

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© 2014 Springer-Verlag Berlin Heidelberg

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Olano, C., Méndez, C., Salas, J.A. (2014). Strategies for the Design and Discovery of Novel Antibiotics using Genetic Engineering and Genome Mining. In: Villa, T., Veiga-Crespo, P. (eds) Antimicrobial Compounds. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40444-3_1

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