Cargando…
Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids
Sesquiterpenoids are important secondary metabolites with various pharma- and nutraceutical properties. In particular, higher basidiomycetes possess a versatile biosynthetic repertoire for these bioactive compounds. To date, only a few microbial production systems for fungal sesquiterpenoids have be...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396576/ https://www.ncbi.nlm.nih.gov/pubmed/32849341 http://dx.doi.org/10.3389/fmicb.2020.01655 |
_version_ | 1783565613977829376 |
---|---|
author | Lee, Jungho Hilgers, Fabienne Loeschke, Anita Jaeger, Karl-Erich Feldbrügge, Michael |
author_facet | Lee, Jungho Hilgers, Fabienne Loeschke, Anita Jaeger, Karl-Erich Feldbrügge, Michael |
author_sort | Lee, Jungho |
collection | PubMed |
description | Sesquiterpenoids are important secondary metabolites with various pharma- and nutraceutical properties. In particular, higher basidiomycetes possess a versatile biosynthetic repertoire for these bioactive compounds. To date, only a few microbial production systems for fungal sesquiterpenoids have been established. Here, we introduce Ustilago maydis as a novel production host. This model fungus is a close relative of higher basidiomycetes. It offers the advantage of metabolic compatibility and potential tolerance for substances toxic to other microorganisms. We successfully implemented a heterologous pathway to produce the carotenoid lycopene that served as a straightforward read-out for precursor pathway engineering. Overexpressing genes encoding enzymes of the mevalonate pathway resulted in increased lycopene levels. Verifying the subcellular localization of the relevant enzymes revealed that initial metabolic reactions might take place in peroxisomes: despite the absence of a canonical peroxisomal targeting sequence, acetyl-CoA C-acetyltransferase Aat1 localized to peroxisomes. By expressing the plant (+)-valencene synthase CnVS and the basidiomycete sesquiterpenoid synthase Cop6, we succeeded in producing (+)-valencene and α-cuprenene, respectively. Importantly, the fungal compound yielded about tenfold higher titers in comparison to the plant substance. This proof of principle demonstrates that U. maydis can serve as promising novel chassis for the production of terpenoids. |
format | Online Article Text |
id | pubmed-7396576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73965762020-08-25 Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids Lee, Jungho Hilgers, Fabienne Loeschke, Anita Jaeger, Karl-Erich Feldbrügge, Michael Front Microbiol Microbiology Sesquiterpenoids are important secondary metabolites with various pharma- and nutraceutical properties. In particular, higher basidiomycetes possess a versatile biosynthetic repertoire for these bioactive compounds. To date, only a few microbial production systems for fungal sesquiterpenoids have been established. Here, we introduce Ustilago maydis as a novel production host. This model fungus is a close relative of higher basidiomycetes. It offers the advantage of metabolic compatibility and potential tolerance for substances toxic to other microorganisms. We successfully implemented a heterologous pathway to produce the carotenoid lycopene that served as a straightforward read-out for precursor pathway engineering. Overexpressing genes encoding enzymes of the mevalonate pathway resulted in increased lycopene levels. Verifying the subcellular localization of the relevant enzymes revealed that initial metabolic reactions might take place in peroxisomes: despite the absence of a canonical peroxisomal targeting sequence, acetyl-CoA C-acetyltransferase Aat1 localized to peroxisomes. By expressing the plant (+)-valencene synthase CnVS and the basidiomycete sesquiterpenoid synthase Cop6, we succeeded in producing (+)-valencene and α-cuprenene, respectively. Importantly, the fungal compound yielded about tenfold higher titers in comparison to the plant substance. This proof of principle demonstrates that U. maydis can serve as promising novel chassis for the production of terpenoids. Frontiers Media S.A. 2020-07-24 /pmc/articles/PMC7396576/ /pubmed/32849341 http://dx.doi.org/10.3389/fmicb.2020.01655 Text en Copyright © 2020 Lee, Hilgers, Loeschke, Jaeger and Feldbrügge. 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) and the copyright owner(s) 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 Lee, Jungho Hilgers, Fabienne Loeschke, Anita Jaeger, Karl-Erich Feldbrügge, Michael Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids |
title | Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids |
title_full | Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids |
title_fullStr | Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids |
title_full_unstemmed | Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids |
title_short | Ustilago maydis Serves as a Novel Production Host for the Synthesis of Plant and Fungal Sesquiterpenoids |
title_sort | ustilago maydis serves as a novel production host for the synthesis of plant and fungal sesquiterpenoids |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396576/ https://www.ncbi.nlm.nih.gov/pubmed/32849341 http://dx.doi.org/10.3389/fmicb.2020.01655 |
work_keys_str_mv | AT leejungho ustilagomaydisservesasanovelproductionhostforthesynthesisofplantandfungalsesquiterpenoids AT hilgersfabienne ustilagomaydisservesasanovelproductionhostforthesynthesisofplantandfungalsesquiterpenoids AT loeschkeanita ustilagomaydisservesasanovelproductionhostforthesynthesisofplantandfungalsesquiterpenoids AT jaegerkarlerich ustilagomaydisservesasanovelproductionhostforthesynthesisofplantandfungalsesquiterpenoids AT feldbruggemichael ustilagomaydisservesasanovelproductionhostforthesynthesisofplantandfungalsesquiterpenoids |