Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> Strain

RES-701-3 and RES-701-4 are two class II lasso peptides originally identified in the fermentation broth of <i>Streptomyces</i> sp. RE-896, which have been described as selective endothelin type B receptor antagonists. These two lasso peptides only differ in the identity of the C-terminal...

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Main Authors: Daniel Oves-Costales, Marina Sánchez-Hidalgo, Jesús Martín, Olga Genilloud
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/18/5/238
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spelling doaj-f417317d32854deca9fc4cf0dcba276b2020-11-25T04:05:15ZengMDPI AGMarine Drugs1660-33972020-05-011823823810.3390/md18050238Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> StrainDaniel Oves-Costales0Marina Sánchez-Hidalgo1Jesús Martín2Olga Genilloud3Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Avda del Conocimiento 34, 18016 Armilla (Granada), SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Avda del Conocimiento 34, 18016 Armilla (Granada), SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Avda del Conocimiento 34, 18016 Armilla (Granada), SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Avda del Conocimiento 34, 18016 Armilla (Granada), SpainRES-701-3 and RES-701-4 are two class II lasso peptides originally identified in the fermentation broth of <i>Streptomyces</i> sp. RE-896, which have been described as selective endothelin type B receptor antagonists. These two lasso peptides only differ in the identity of the C-terminal residue (tryptophan in RES-701-3, 7-hydroxy-tryptophan in RES-701-4), thus raising an intriguing question about the mechanism behind the modification of the tryptophan residue. In this study, we describe the identification of their biosynthetic gene cluster through the genome mining of the marine actinomycete <i>Streptomyces caniferus</i> CA-271066, its cloning and heterologous expression, and show that the seven open reading frames (ORFs) encoded within the gene cluster are sufficient for the biosynthesis of both lasso peptides. We propose that ResE, a protein lacking known putatively conserved domains, is likely to play a key role in the post-translational modification of the C-terminal tryptophan of RES-701-3 that affords RES-701-4. A BLASTP search with the ResE amino acid sequence shows the presence of homologues of this protein in the genomes of eight other <i>Streptomyces</i> strains, which also harbour the genes encoding the RES-701-3, -4 precursor peptide, split-B proteins and ATP-dependent lactam synthetase required for the biosynthesis of these compounds.https://www.mdpi.com/1660-3397/18/5/238lasso peptideRES-701-3RES-701-4genome miningbiosynthetic gene cluster<i>Streptomyces caniferus</i>
collection DOAJ
language English
format Article
sources DOAJ
author Daniel Oves-Costales
Marina Sánchez-Hidalgo
Jesús Martín
Olga Genilloud
spellingShingle Daniel Oves-Costales
Marina Sánchez-Hidalgo
Jesús Martín
Olga Genilloud
Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> Strain
Marine Drugs
lasso peptide
RES-701-3
RES-701-4
genome mining
biosynthetic gene cluster
<i>Streptomyces caniferus</i>
author_facet Daniel Oves-Costales
Marina Sánchez-Hidalgo
Jesús Martín
Olga Genilloud
author_sort Daniel Oves-Costales
title Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> Strain
title_short Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> Strain
title_full Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> Strain
title_fullStr Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> Strain
title_full_unstemmed Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine <i>Streptomyces</i> Strain
title_sort identification, cloning and heterologous expression of the gene cluster directing res-701-3, -4 lasso peptides biosynthesis from a marine <i>streptomyces</i> strain
publisher MDPI AG
series Marine Drugs
issn 1660-3397
publishDate 2020-05-01
description RES-701-3 and RES-701-4 are two class II lasso peptides originally identified in the fermentation broth of <i>Streptomyces</i> sp. RE-896, which have been described as selective endothelin type B receptor antagonists. These two lasso peptides only differ in the identity of the C-terminal residue (tryptophan in RES-701-3, 7-hydroxy-tryptophan in RES-701-4), thus raising an intriguing question about the mechanism behind the modification of the tryptophan residue. In this study, we describe the identification of their biosynthetic gene cluster through the genome mining of the marine actinomycete <i>Streptomyces caniferus</i> CA-271066, its cloning and heterologous expression, and show that the seven open reading frames (ORFs) encoded within the gene cluster are sufficient for the biosynthesis of both lasso peptides. We propose that ResE, a protein lacking known putatively conserved domains, is likely to play a key role in the post-translational modification of the C-terminal tryptophan of RES-701-3 that affords RES-701-4. A BLASTP search with the ResE amino acid sequence shows the presence of homologues of this protein in the genomes of eight other <i>Streptomyces</i> strains, which also harbour the genes encoding the RES-701-3, -4 precursor peptide, split-B proteins and ATP-dependent lactam synthetase required for the biosynthesis of these compounds.
topic lasso peptide
RES-701-3
RES-701-4
genome mining
biosynthetic gene cluster
<i>Streptomyces caniferus</i>
url https://www.mdpi.com/1660-3397/18/5/238
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