Cargando…
Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P
Genome mining of the mithramycin producer Streptomyces argillaceus ATCC 12956 revealed 31 gene clusters for the biosynthesis of secondary metabolites, and allowed to predict the encoded products for 11 of these clusters. Cluster 18 (renamed cluster arp) corresponded to a type I polyketide gene clust...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300972/ https://www.ncbi.nlm.nih.gov/pubmed/28239372 http://dx.doi.org/10.3389/fmicb.2017.00194 |
_version_ | 1782506273768472576 |
---|---|
author | Ye, Suhui Molloy, Brian Braña, Alfredo F. Zabala, Daniel Olano, Carlos Cortés, Jesús Morís, Francisco Salas, José A. Méndez, Carmen |
author_facet | Ye, Suhui Molloy, Brian Braña, Alfredo F. Zabala, Daniel Olano, Carlos Cortés, Jesús Morís, Francisco Salas, José A. Méndez, Carmen |
author_sort | Ye, Suhui |
collection | PubMed |
description | Genome mining of the mithramycin producer Streptomyces argillaceus ATCC 12956 revealed 31 gene clusters for the biosynthesis of secondary metabolites, and allowed to predict the encoded products for 11 of these clusters. Cluster 18 (renamed cluster arp) corresponded to a type I polyketide gene cluster related to the previously described coelimycin P1 and streptazone gene clusters. The arp cluster consists of fourteen genes, including genes coding for putative regulatory proteins (a SARP-like transcriptional activator and a TetR-like transcriptional repressor), genes coding for structural proteins (three PKSs, one aminotransferase, two dehydrogenases, two cyclases, one imine reductase, a type II thioesterase, and a flavin reductase), and one gene coding for a hypothetical protein. Identification of encoded compounds by this cluster was achieved by combining several strategies: (i) inactivation of the type I PKS gene arpPIII; (ii) inactivation of the putative TetR-transcriptional repressor arpRII; (iii) cultivation of strains in different production media; and (iv) using engineered strains with higher intracellular concentration of malonyl-CoA. This has allowed identifying six new alkaloid compounds named argimycins P, which were purified and structurally characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. Some argimycins P showed a piperidine ring with a polyene side chain (argimycin PIX); others contain also a fused five-membered ring (argimycins PIV-PVI). Argimycins PI-PII showed a pyridine ring instead, and an additional N-acetylcysteinyl moiety. These compounds seem to play a negative role in growth and colony differentiation in S. argillaceus, and some of them show weak antibiotic activity. A pathway for the biosynthesis of argimycins P is proposed, based on the analysis of proposed enzyme functions and on the structure of compounds encoded by the arp cluster. |
format | Online Article Text |
id | pubmed-5300972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53009722017-02-24 Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P Ye, Suhui Molloy, Brian Braña, Alfredo F. Zabala, Daniel Olano, Carlos Cortés, Jesús Morís, Francisco Salas, José A. Méndez, Carmen Front Microbiol Microbiology Genome mining of the mithramycin producer Streptomyces argillaceus ATCC 12956 revealed 31 gene clusters for the biosynthesis of secondary metabolites, and allowed to predict the encoded products for 11 of these clusters. Cluster 18 (renamed cluster arp) corresponded to a type I polyketide gene cluster related to the previously described coelimycin P1 and streptazone gene clusters. The arp cluster consists of fourteen genes, including genes coding for putative regulatory proteins (a SARP-like transcriptional activator and a TetR-like transcriptional repressor), genes coding for structural proteins (three PKSs, one aminotransferase, two dehydrogenases, two cyclases, one imine reductase, a type II thioesterase, and a flavin reductase), and one gene coding for a hypothetical protein. Identification of encoded compounds by this cluster was achieved by combining several strategies: (i) inactivation of the type I PKS gene arpPIII; (ii) inactivation of the putative TetR-transcriptional repressor arpRII; (iii) cultivation of strains in different production media; and (iv) using engineered strains with higher intracellular concentration of malonyl-CoA. This has allowed identifying six new alkaloid compounds named argimycins P, which were purified and structurally characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. Some argimycins P showed a piperidine ring with a polyene side chain (argimycin PIX); others contain also a fused five-membered ring (argimycins PIV-PVI). Argimycins PI-PII showed a pyridine ring instead, and an additional N-acetylcysteinyl moiety. These compounds seem to play a negative role in growth and colony differentiation in S. argillaceus, and some of them show weak antibiotic activity. A pathway for the biosynthesis of argimycins P is proposed, based on the analysis of proposed enzyme functions and on the structure of compounds encoded by the arp cluster. Frontiers Media S.A. 2017-02-10 /pmc/articles/PMC5300972/ /pubmed/28239372 http://dx.doi.org/10.3389/fmicb.2017.00194 Text en Copyright © 2017 Ye, Molloy, Braña, Zabala, Olano, Cortés, Morís, Salas and Méndez. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Ye, Suhui Molloy, Brian Braña, Alfredo F. Zabala, Daniel Olano, Carlos Cortés, Jesús Morís, Francisco Salas, José A. Méndez, Carmen Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P |
title | Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P |
title_full | Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P |
title_fullStr | Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P |
title_full_unstemmed | Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P |
title_short | Identification by Genome Mining of a Type I Polyketide Gene Cluster from Streptomyces argillaceus Involved in the Biosynthesis of Pyridine and Piperidine Alkaloids Argimycins P |
title_sort | identification by genome mining of a type i polyketide gene cluster from streptomyces argillaceus involved in the biosynthesis of pyridine and piperidine alkaloids argimycins p |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300972/ https://www.ncbi.nlm.nih.gov/pubmed/28239372 http://dx.doi.org/10.3389/fmicb.2017.00194 |
work_keys_str_mv | AT yesuhui identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT molloybrian identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT branaalfredof identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT zabaladaniel identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT olanocarlos identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT cortesjesus identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT morisfrancisco identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT salasjosea identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp AT mendezcarmen identificationbygenomeminingofatypeipolyketidegeneclusterfromstreptomycesargillaceusinvolvedinthebiosynthesisofpyridineandpiperidinealkaloidsargimycinsp |