Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivorans

ABSTRACT The isoprenoid bisabolene, one of the simplest monocyclic sesquiterpenes, is a natural plant product that, in addition to its biological function, serves as a precursor for many industrial products. Due to the low concentration of bisabolene and the long harvest cycle, industrial production...

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Main Authors: Andrea Mentrup, Luca V. Scheitz, Theo Wallenfang, Michael Rother
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Microbial Biotechnology
Subjects:
Online Access:https://doi.org/10.1111/1751-7915.70105
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author Andrea Mentrup
Luca V. Scheitz
Theo Wallenfang
Michael Rother
author_facet Andrea Mentrup
Luca V. Scheitz
Theo Wallenfang
Michael Rother
author_sort Andrea Mentrup
collection DOAJ
description ABSTRACT The isoprenoid bisabolene, one of the simplest monocyclic sesquiterpenes, is a natural plant product that, in addition to its biological function, serves as a precursor for many industrial products. Due to the low concentration of bisabolene and the long harvest cycle, industrial production of this isoprenoid in plants is economically challenging. Chemical synthesis of bisabolene also suffers from significant disadvantages, such as low yields, toxic side products and high costs. Archaea appear suitable producers of isoprenoids, as their membrane lipids consist of isoprenoid ethers, which are synthesised via a variant of the mevalonate (MVA) pathway. Archaeal model species have versatile metabolic capacities, which makes them potential candidates for biotechnological applications. Here, we engineered Methanosarcina acetivorans for production of α‐bisabolene from one‐carbon substrates by introducing a bisabolene synthase from Abies grandis. Expression of a codon‐optimised bisabolene synthase gene in M. acetivorans resulted in 10.6 mg bisabolene/L of culture. Overexpressing genes of the MVA pathway only slightly increased bisabolene yields, which, however, were reached much earlier during incubations than in the corresponding parent strain. The data presented argue for the suitability of M. acetivorans for the biotechnical production of certain isoprenoids.
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spelling doaj-art-d062f36c84464de4afdc5d5e7658abfe2025-08-20T02:32:19ZengWileyMicrobial Biotechnology1751-79152025-02-01182n/an/a10.1111/1751-7915.70105Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivoransAndrea Mentrup0Luca V. Scheitz1Theo Wallenfang2Michael Rother3Fakultät Biologie Technische Universität Dresden Dresden GermanyFakultät Biologie Technische Universität Dresden Dresden GermanyFakultät Biologie Technische Universität Dresden Dresden GermanyFakultät Biologie Technische Universität Dresden Dresden GermanyABSTRACT The isoprenoid bisabolene, one of the simplest monocyclic sesquiterpenes, is a natural plant product that, in addition to its biological function, serves as a precursor for many industrial products. Due to the low concentration of bisabolene and the long harvest cycle, industrial production of this isoprenoid in plants is economically challenging. Chemical synthesis of bisabolene also suffers from significant disadvantages, such as low yields, toxic side products and high costs. Archaea appear suitable producers of isoprenoids, as their membrane lipids consist of isoprenoid ethers, which are synthesised via a variant of the mevalonate (MVA) pathway. Archaeal model species have versatile metabolic capacities, which makes them potential candidates for biotechnological applications. Here, we engineered Methanosarcina acetivorans for production of α‐bisabolene from one‐carbon substrates by introducing a bisabolene synthase from Abies grandis. Expression of a codon‐optimised bisabolene synthase gene in M. acetivorans resulted in 10.6 mg bisabolene/L of culture. Overexpressing genes of the MVA pathway only slightly increased bisabolene yields, which, however, were reached much earlier during incubations than in the corresponding parent strain. The data presented argue for the suitability of M. acetivorans for the biotechnical production of certain isoprenoids.https://doi.org/10.1111/1751-7915.70105bisaboleneengineeringisoprenoidsMethanosarcinamevalonate pathway
spellingShingle Andrea Mentrup
Luca V. Scheitz
Theo Wallenfang
Michael Rother
Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivorans
Microbial Biotechnology
bisabolene
engineering
isoprenoids
Methanosarcina
mevalonate pathway
title Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivorans
title_full Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivorans
title_fullStr Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivorans
title_full_unstemmed Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivorans
title_short Production of the Sesquiterpene Bisabolene From One‐ and Two‐Carbon Compounds in Engineered Methanosarcina acetivorans
title_sort production of the sesquiterpene bisabolene from one and two carbon compounds in engineered methanosarcina acetivorans
topic bisabolene
engineering
isoprenoids
Methanosarcina
mevalonate pathway
url https://doi.org/10.1111/1751-7915.70105
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