Journal
FRONTIERS IN MICROBIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2018.00252
Keywords
type I polyketide synthase; pyridine; piperidine; piperideine; imine reductase; specialized metabolites; regulation; alkaloid
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Funding
- Spanish Ministry of Economy and Competitiveness, MINECO [BIO2011-25398, BIO2014-56752-R, PIM2010EEI-00752]
- grant Apoyo a Grupos de Excelencia, Principado de Asturias-FEDER [FC-15-GRUPIN14-014]
- ERA-IB program
- MINECO [PIM2010EEI-00752]
- MINECO
- Fundacion Bancaria Cajastur
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Argimycins P are a recently identified family of polyketide alkaloids encoded by the cryptic gene cluster arp of Streptomyces argillaceus. These compounds contain either a piperideine ring, or a piperidine ring which may be fused to a five membered ring, and a polyene side chain, which is bound in some cases to an N-acetylcysteine moiety. The arp cluster consists of 11 genes coding for structural proteins, two for regulatory proteins and one for a hypothetical protein. Herein, we have characterized the post-piperideine ring biosynthesis steps of argimycins P through the generation of mutants in arp genes, the identification and characterization of compounds accumulated by those mutants, and cross-feeding experiments between mutants. Based in these results, a biosynthesis pathway is proposed assigning roles to every arp gene product. The regulation of the arp cluster is also addressed by inactivating/overexpressing the positive SARP-like arpRI and the negative TetR-like arpRII transcriptional regulators and determining the effect on argimycins P production, and through gene expression analyses (reverse transcription PCR and quantitative real-time PCR) of arp genes in regulatory mutants in comparison to the wild type strain. These findings will contribute to deepen the knowledge on the biosynthesis of piperidine-containing polyketides and provide tools that can be used to generate new analogs by genetic engineering and/or biocatalysis.
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