Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches

Adriana Becerril; Susana Álvarez; Alfredo F Braña; Sergio Rico; Margarita Díaz; Ramón I Santamaría; José A Salas; Carmen Méndez

doi:10.1371/journal.pone.0198145

Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches

PLoS One. 2018 May 24;13(5):e0198145. doi: 10.1371/journal.pone.0198145. eCollection 2018.

Authors

Adriana Becerril^{1

2}, Susana Álvarez¹, Alfredo F Braña^{1

2}, Sergio Rico³, Margarita Díaz³, Ramón I Santamaría³, José A Salas^{1

2}, Carmen Méndez^{1

2}

Affiliations

¹ Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, Oviedo, Spain.
² Instituto de Investigación Sanitaria de Asturias (ISPA), Oviedo, Spain.
³ Departamento de Microbiología y Genética, Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, Salamanca, Spain.

Abstract

Sequencing of Streptomyces genomes has revealed they harbor a high number of biosynthesis gene cluster (BGC), which uncovered their enormous potentiality to encode specialized metabolites. However, these metabolites are not usually produced under standard laboratory conditions. In this manuscript we report the activation of BGCs for antimycins, carotenoids, germicidins and desferrioxamine compounds in Streptomyces argillaceus, and the identification of the encoded compounds. This was achieved by following different strategies, including changing the growth conditions, heterologous expression of the cluster and inactivating the adpAa or overexpressing the abrC3 global regulatory genes. In addition, three new carotenoid compounds have been identified.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimycin A / analogs & derivatives*
Antimycin A / metabolism
Carotenoids / metabolism*
Deferoxamine / metabolism*
Gene Expression Regulation, Bacterial
Multigene Family*
Phenols / metabolism*
Pyrones / metabolism*
Streptomyces / genetics*
Streptomyces / growth & development
Streptomyces / metabolism*

Substances

Phenols
Pyrones
isorenieratene
antimycin
germicidin
Carotenoids
Antimycin A
Deferoxamine

Grants and funding

This work was supported by grants from the Spanish Ministry of Economy and Competitiveness, MINECO (Grants BIO2011-25398, BIO2014-56752-R and PIM2010EEI-00752 to CM), and by the grant “Apoyo a grupos de excelencia”, Principado de Asturias-FEDER (FC-15-GRUPIN14-014). AB and SA were recipient of predoctoral fellowships from MINECO. RS and MD acknowledge funding from BIO2015-66958-R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.