Matabaro_2021_Sci.Rep_11_3541

Reference

Title : Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A - Matabaro_2021_Sci.Rep_11_3541
Author(s) : Matabaro E , Kaspar H , Dahlin P , Bader DLV , Murar CE , Staubli F , Field CM , Bode JW , Kunzler M
Ref : Sci Rep , 11 :3541 , 2021
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 alpha-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.

PubMedSearch : Matabaro_2021_Sci.Rep_11_3541
PubMedID: 33574430
Gene_locus related to this paper: ompol-OphP

Citations formats

Matabaro E, Kaspar H, Dahlin P, Bader DLV, Murar CE, Staubli F, Field CM, Bode JW, Kunzler M (2021)
Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A
Sci Rep 11 :3541

Matabaro E, Kaspar H, Dahlin P, Bader DLV, Murar CE, Staubli F, Field CM, Bode JW, Kunzler M (2021)
Sci Rep 11 :3541