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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ye, Suhui, Molloy, Brian, Braña, Alfredo F., Zabala, Daniel, Olano, Carlos, Cortés, Jesús, Morís, Francisco, Salas, José A., Méndez, Carmen
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