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Recapitulation of the evolution of biosynthetic gene clusters reveals hidden chemical diversity on bacterial genomes

Pablo Cruz-Morales, Christian E. Martínez-Guerrero, Marco A. Morales-Escalante, Luis Yáñez-Guerra, Johannes Florian Kopp, Jörg Feldmann, Hilda E. Ramos-Aboites, Francisco Barona-Gómez
doi: https://doi.org/10.1101/020503
Pablo Cruz-Morales
1Evolution of Metabolic Diversity Laboratory, Langebio, Cinvestav-IPN. Irapuato, Guanajuato, México.
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  • For correspondence: fbarona@langebio.cinvestav.mx pcruz@langebio.cinvestav.mx
Christian E. Martínez-Guerrero
1Evolution of Metabolic Diversity Laboratory, Langebio, Cinvestav-IPN. Irapuato, Guanajuato, México.
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Marco A. Morales-Escalante
1Evolution of Metabolic Diversity Laboratory, Langebio, Cinvestav-IPN. Irapuato, Guanajuato, México.
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Luis Yáñez-Guerra
1Evolution of Metabolic Diversity Laboratory, Langebio, Cinvestav-IPN. Irapuato, Guanajuato, México.
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Johannes Florian Kopp
2Trace Element Speciation Laboratory (TESLA), College of Physical Sciences. Aberdeen, Scotland, UK.
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Jörg Feldmann
2Trace Element Speciation Laboratory (TESLA), College of Physical Sciences. Aberdeen, Scotland, UK.
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Hilda E. Ramos-Aboites
1Evolution of Metabolic Diversity Laboratory, Langebio, Cinvestav-IPN. Irapuato, Guanajuato, México.
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Francisco Barona-Gómez
1Evolution of Metabolic Diversity Laboratory, Langebio, Cinvestav-IPN. Irapuato, Guanajuato, México.
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  • For correspondence: fbarona@langebio.cinvestav.mx pcruz@langebio.cinvestav.mx
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Abstract

Natural products have provided humans with antibiotics for millennia. However, a decline in the pace of chemical discovery exerts pressure on human health as antibiotic resistance spreads. The empirical nature of current genome mining approaches used for natural products research limits the chemical space that is explored. By integration of evolutionary concepts related to emergence of metabolism, we have gained fundamental insights that are translated into an alternative genome mining approach, termed EvoMining. As the founding assumption of EvoMining is the evolution of enzymes, we solved two milestone problems revealing unprecedented conversions. First, we report the biosynthetic gene cluster of the ‘orphan’ metabolite leupeptin in Streptomyces roseus. Second, we discover an enzyme involved in formation of an arsenic-carbon bond in Streptomyces coelicolor and Streptomyces lividans. This work provides evidence that bacterial chemical repertoire is underexploited, as well as an approach to accelerate the discovery of novel antibiotics from bacterial genomes.

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Posted July 06, 2015.
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Recapitulation of the evolution of biosynthetic gene clusters reveals hidden chemical diversity on bacterial genomes
Pablo Cruz-Morales, Christian E. Martínez-Guerrero, Marco A. Morales-Escalante, Luis Yáñez-Guerra, Johannes Florian Kopp, Jörg Feldmann, Hilda E. Ramos-Aboites, Francisco Barona-Gómez
bioRxiv 020503; doi: https://doi.org/10.1101/020503
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Recapitulation of the evolution of biosynthetic gene clusters reveals hidden chemical diversity on bacterial genomes
Pablo Cruz-Morales, Christian E. Martínez-Guerrero, Marco A. Morales-Escalante, Luis Yáñez-Guerra, Johannes Florian Kopp, Jörg Feldmann, Hilda E. Ramos-Aboites, Francisco Barona-Gómez
bioRxiv 020503; doi: https://doi.org/10.1101/020503

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