Mentrup Andrea, Scheitz Luca V, Wallenfang Theo, Rother Michael
Fakultät Biologie, Technische Universität Dresden, Dresden, Germany.
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Microb Biotechnol. 2025 Feb;18(2):e70105. doi: 10.1111/1751-7915.70105.
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.
类异戊二烯红没药烯是最简单的单环倍半萜之一,是一种天然植物产物,除了具有生物学功能外,还是许多工业产品的前体。由于红没药烯浓度低且收获周期长,在植物中进行这种类异戊二烯的工业生产在经济上具有挑战性。红没药烯的化学合成也存在重大缺点,如产率低、有毒副产物和成本高。古菌似乎是类异戊二烯的合适生产者,因为它们的膜脂由类异戊二烯醚组成,这些醚是通过甲羟戊酸(MVA)途径的变体合成的。古菌模式物种具有多种代谢能力,这使其成为生物技术应用的潜在候选者。在这里,我们通过引入来自巨冷杉的红没药烯合酶,对嗜乙酸甲烷八叠球菌进行工程改造,使其能够从一碳底物生产α-红没药烯。在嗜乙酸甲烷八叠球菌中表达密码子优化的红没药烯合酶基因,导致培养物中红没药烯的产量达到10.6毫克/升。过表达MVA途径的基因仅略微提高了红没药烯的产量,然而,在培养过程中比相应的亲本菌株更早达到这一产量。所呈现的数据表明嗜乙酸甲烷八叠球菌适合用于某些类异戊二烯的生物技术生产。