Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A

Abstract Backbone N-methylation and macrocyclization improve the pharmacological properties of peptides by enhancing their proteolytic stability, membrane permeability and target selectivity. Borosins are backbone N-methylated peptide macrocycles derived from a precursor protein which contains a pep...

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Autores principales:	Emmanuel Matabaro, Hannelore Kaspar, Paul Dahlin, Daniel L. V. Bader, Claudia E. Murar, Florian Staubli, Christopher M. Field, Jeffrey W. Bode, Markus Künzler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ea7352d2f614b6baa94eeac5342cde2
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spelling	oai:doaj.org-article:8ea7352d2f614b6baa94eeac5342cde22021-12-02T13:30:10ZIdentification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A10.1038/s41598-021-83106-22045-2322https://doaj.org/article/8ea7352d2f614b6baa94eeac5342cde22021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83106-2https://doaj.org/toc/2045-2322Abstract Backbone N-methylation and macrocyclization improve the pharmacological properties of peptides by enhancing their proteolytic stability, membrane permeability and target selectivity. Borosins are backbone N-methylated peptide macrocycles derived from a precursor protein which contains a peptide α-N-methyltransferase domain autocatalytically modifying the core peptide located at its C-terminus. Founding members of borosins are the omphalotins from the mushroom Omphalotus olearius (omphalotins A-I) with nine out of 12 L-amino acids being backbone N-methylated. The omphalotin biosynthetic gene cluster codes for the precursor protein OphMA, the protease prolyloligopeptidase OphP and other proteins that are likely to be involved in other post-translational modifications of the peptide. Mining of available fungal genome sequences revealed the existence of highly homologous gene clusters in the basidiomycetes Lentinula edodes and Dendrothele bispora. The respective borosins, referred to as lentinulins and dendrothelins are naturally produced by L. edodes and D. bispora as shown by analysis of respective mycelial extracts. We produced all three homologous peptide natural products by coexpression of OphMA hybrid proteins and OphP in the yeast Pichia pastoris. The recombinant peptides differ in their nematotoxic activity against the plant pathogen Meloidogyne incognita. Our findings pave the way for the production of borosin peptide natural products and their potential application as novel biopharmaceuticals and biopesticides.Emmanuel MatabaroHannelore KasparPaul DahlinDaniel L. V. BaderClaudia E. MurarFlorian StaubliChristopher M. FieldJeffrey W. BodeMarkus KünzlerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emmanuel Matabaro Hannelore Kaspar Paul Dahlin Daniel L. V. Bader Claudia E. Murar Florian Staubli Christopher M. Field Jeffrey W. Bode Markus Künzler Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A
description	Abstract Backbone N-methylation and macrocyclization improve the pharmacological properties of peptides by enhancing their proteolytic stability, membrane permeability and target selectivity. Borosins are backbone N-methylated peptide macrocycles derived from a precursor protein which contains a peptide α-N-methyltransferase domain autocatalytically modifying the core peptide located at its C-terminus. Founding members of borosins are the omphalotins from the mushroom Omphalotus olearius (omphalotins A-I) with nine out of 12 L-amino acids being backbone N-methylated. The omphalotin biosynthetic gene cluster codes for the precursor protein OphMA, the protease prolyloligopeptidase OphP and other proteins that are likely to be involved in other post-translational modifications of the peptide. Mining of available fungal genome sequences revealed the existence of highly homologous gene clusters in the basidiomycetes Lentinula edodes and Dendrothele bispora. The respective borosins, referred to as lentinulins and dendrothelins are naturally produced by L. edodes and D. bispora as shown by analysis of respective mycelial extracts. We produced all three homologous peptide natural products by coexpression of OphMA hybrid proteins and OphP in the yeast Pichia pastoris. The recombinant peptides differ in their nematotoxic activity against the plant pathogen Meloidogyne incognita. Our findings pave the way for the production of borosin peptide natural products and their potential application as novel biopharmaceuticals and biopesticides.
format	article
author	Emmanuel Matabaro Hannelore Kaspar Paul Dahlin Daniel L. V. Bader Claudia E. Murar Florian Staubli Christopher M. Field Jeffrey W. Bode Markus Künzler
author_facet	Emmanuel Matabaro Hannelore Kaspar Paul Dahlin Daniel L. V. Bader Claudia E. Murar Florian Staubli Christopher M. Field Jeffrey W. Bode Markus Künzler
author_sort	Emmanuel Matabaro
title	Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A
title_short	Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A
title_full	Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A
title_fullStr	Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A
title_full_unstemmed	Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A
title_sort	identification, heterologous production and bioactivity of lentinulin a and dendrothelin a, two natural variants of backbone n-methylated peptide macrocycle omphalotin a
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ea7352d2f614b6baa94eeac5342cde2
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Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A

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