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PMID: 24593309 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Activation and identification of five clusters for secondary metabolites in Streptomyces albus J1074.

Microbial biotechnology ·Vol. 7 ·No. 3 ·2014-05-00 ·Pages 242-56

Olano C, García I, González A, Rodriguez M, Rozas D, Rubio J, Sánchez-Hidalgo M, Braña AF, Méndez C, Salas JA

Abstract

Streptomyces albus J1074 is a streptomycete strain widely used as a host for expression of secondary metabolite gene clusters. Bioinformatic analysis of the genome of this organism predicts the presence of 27 gene clusters for secondary metabolites. We have used three different strategies for the activation of some of these silent/cryptic gene clusters in S. albus J1074: two hybrid polyketide-non-ribosomal peptides (PK-NRP) (antimycin and 6-epi-alteramides), a type I PK (candicidin), a non-ribosomal peptides (NRP) (indigoidine) and glycosylated compounds (paulomycins). By insertion of a strong and constitutive promoter in front of selected genes of two clusters, production of the blue pigment indigoidine and of two novel members of the polycyclic tetramate macrolactam family (6-epi-alteramides A and B) was activated. Overexpression of positive regulatory genes from the same organism also activated the biosynthesis of 6-epi-alteramides and heterologous expression of the regulatory gene pimM of the pimaricin cluster activated the simultaneous production of candicidins and antimycins, suggesting some kind of cross-regulation between both clusters. A cluster for glycosylated compounds (paulomycins) was also identified by comparison of the high-performance liquid chromatography profiles of the wild-type strain with that of a mutant in which two key enzymes of the cluster were simultaneously deleted.

MeSH Terms
Biological Products/metabolism Gene Expression Multigene Family Mutagenesis, Insertional Recombination, Genetic Secondary Metabolism Streptomyces/genetics,metabolism
Chemicals
Biological Products
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Olano Carlos
Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, Oviedo, Spain.
García Ignacio
González Aranzazu
Rodriguez Miriam
Rozas Daniel
Rubio Julio
Sánchez-Hidalgo Marina
Braña Alfredo F
Méndez Carmen
Salas José A
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Article Info
Journal
Microbial biotechnology
Abbr.
Microb Biotechnol
ISSN
1751-7915
DOI
10.1111/1751-7915.12116
Published
2014-05-00
Epub
2014-00-04
Pages
242-56
Language
English
Region
United States
NLM ID
101316335
PMCID
PMC3992020
Subset
IM
External Links
PubMed source DOI: 10.1111/1751-7915.12116 PMC Full Text View journal details
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