RESEARCH ARTICLE Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches Adriana Becerril1,2, Susana A lvarez1, Alfredo F. Braña1,2, Sergio Rico3, Margarita DõÂaz3, a1111111111 RamoÂn I. SantamarõÂa3, Jose A. Salas1,2, Carmen MeÂndez1,2* a1111111111 a1111111111 1 Departamento de BiologõÂa Funcional e Instituto Universitario de OncologõÂa del Principado de Asturias (I.U. O.P.A), Universidad de Oviedo, Oviedo, Spain, 2 Instituto de InvestigacioÂn Sanitaria de Asturias (ISPA), a1111111111 Oviedo, Spain, 3 Departamento de MicrobiologõÂa y GeneÂtica, Instituto de BiologõÂa Funcional y GenoÂmica, a1111111111 Consejo Superior de Investigaciones CientõÂficas (CSIC)/Universidad de Salamanca, Salamanca, Spain *
[email protected] OPEN ACCESS Abstract Citation: Becerril A, AÂlvarez S, Braña AF, Rico S, DõÂaz M, SantamarõÂa RI, et al. (2018) Uncovering Sequencing of Streptomyces genomes has revealed they harbor a high number of biosyn- production of specialized metabolites by thesis gene cluster (BGC), which uncovered their enormous potentiality to encode special- Streptomyces argillaceus: Activation of cryptic ized metabolites. However, these metabolites are not usually produced under standard biosynthesis gene clusters using nutritional and genetic approaches. PLoS ONE 13(5): e0198145. laboratory conditions. In this manuscript we report the activation of BGCs for antimycins, https://doi.org/10.1371/journal.pone.0198145 carotenoids, germicidins and desferrioxamine compounds in Streptomyces argillaceus, and Editor: Marie-Joelle Virolle, Universite Paris-Sud, the identification of the encoded compounds. This was achieved by following different strat- FRANCE egies, including changing the growth conditions, heterologous expression of the cluster and Received: March 23, 2018 inactivating the adpAa or overexpressing the abrC3 global regulatory genes.