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.
Highlights
Actinomycetes are Gram-positive bacteria belonging to the phylum Actinobacteria, one of the largest taxonomic groups within the domain Bacteria (Gao and Gupta, 2012)
We describe the identification of several compounds produced by S. albus J1074 using genome-mining approaches and activation of the expression of the corresponding gene clusters
At the time the genome sequence was released, no production of secondary metabolites had been reported in S. albus J1074
Summary
Actinomycetes are Gram-positive bacteria belonging to the phylum Actinobacteria, one of the largest taxonomic groups within the domain Bacteria (Gao and Gupta, 2012). Actinobacteria are widely distributed in terrestrial, especially soil, and aquatic ecosystems (McCarthy and Williams, 1992; Stach and Bull, 2005) They are important for soil formation by decomposing and recycling complex mixtures of polymers in dead plant, animal and fungal materials using extracellular enzymes (McCarthy and Williams, 1992). They exhibit diverse physiological and metabolic properties, such as the production of volatile substances (Gust et al, 2003) and a wide variety of secondary metabolites, many of which are potent antibiotic, antifungal, antitumor, immunosuppressant, antiviral or antiparasitic agents. This has turned actinomycetes into the primary bioactive metabolite-producing organisms exploited by the pharmaceutical industry and has prompted the study of these microorganisms at all levels: taxonomy, genetics and physiology (Hopwood, 1999)
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