Cargando…

Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes

The aromatic polyketide 3,5-dimethylorsellinic acid (DMOA) serves as a precursor for many fungal meroterpenoids. A large portion of DMOA-derived meroterpenoids are biosynthesized via the cyclization of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester (1). Theoretically, although 1 can be cyclized into many...

Descripción completa

Detalles Bibliográficos
Autores principales: Tang, Jia, Matsuda, Yudai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473517/
https://www.ncbi.nlm.nih.gov/pubmed/36277653
http://dx.doi.org/10.1039/d2sc02994d
_version_ 1784789520047144960
author Tang, Jia
Matsuda, Yudai
author_facet Tang, Jia
Matsuda, Yudai
author_sort Tang, Jia
collection PubMed
description The aromatic polyketide 3,5-dimethylorsellinic acid (DMOA) serves as a precursor for many fungal meroterpenoids. A large portion of DMOA-derived meroterpenoids are biosynthesized via the cyclization of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester (1). Theoretically, although 1 can be cyclized into many products, only three cyclization modes have been reported. Here, we discovered a meroterpenoid biosynthetic gene cluster in Aspergillus insuetus CBS 107.25, which encodes the biosynthetic enzymes for 1 along with a terpene cyclase that is phylogenetically distantly related to the other characterized cyclases of 1. Intriguingly, InsA7, the terpene cyclase, folds 1 in a pre-boat-chair conformation, generating a new meroterpenoid species with an axially oriented hydroxy group at C3. The A. insuetus strain also harbors an additional gene cluster encoding another cyclase of 1. The second terpene cyclase–InsB2–also synthesizes a new cyclized product of 1, thereby leading to diverging of the biosynthetic pathway in the fungus. Finally, we characterized the tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways.
format Online
Article
Text
id pubmed-9473517
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-94735172022-10-20 Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes Tang, Jia Matsuda, Yudai Chem Sci Chemistry The aromatic polyketide 3,5-dimethylorsellinic acid (DMOA) serves as a precursor for many fungal meroterpenoids. A large portion of DMOA-derived meroterpenoids are biosynthesized via the cyclization of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester (1). Theoretically, although 1 can be cyclized into many products, only three cyclization modes have been reported. Here, we discovered a meroterpenoid biosynthetic gene cluster in Aspergillus insuetus CBS 107.25, which encodes the biosynthetic enzymes for 1 along with a terpene cyclase that is phylogenetically distantly related to the other characterized cyclases of 1. Intriguingly, InsA7, the terpene cyclase, folds 1 in a pre-boat-chair conformation, generating a new meroterpenoid species with an axially oriented hydroxy group at C3. The A. insuetus strain also harbors an additional gene cluster encoding another cyclase of 1. The second terpene cyclase–InsB2–also synthesizes a new cyclized product of 1, thereby leading to diverging of the biosynthetic pathway in the fungus. Finally, we characterized the tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways. The Royal Society of Chemistry 2022-08-17 /pmc/articles/PMC9473517/ /pubmed/36277653 http://dx.doi.org/10.1039/d2sc02994d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Tang, Jia
Matsuda, Yudai
Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
title Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
title_full Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
title_fullStr Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
title_full_unstemmed Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
title_short Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
title_sort discovery of branching meroterpenoid biosynthetic pathways in aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473517/
https://www.ncbi.nlm.nih.gov/pubmed/36277653
http://dx.doi.org/10.1039/d2sc02994d
work_keys_str_mv AT tangjia discoveryofbranchingmeroterpenoidbiosyntheticpathwaysinaspergillusinsuetusinvolvementoftwoterpenecyclaseswithdistinctcyclizationmodes
AT matsudayudai discoveryofbranchingmeroterpenoidbiosyntheticpathwaysinaspergillusinsuetusinvolvementoftwoterpenecyclaseswithdistinctcyclizationmodes