Menaquinone-7 production by engineered Saccharomyces cerevisiae through de novo Synthesis and fermentation optimization.

IF 2.5 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology Letters Pub Date : 2026-09-27 DOI:10.1007/s10529-026-03788-4

Jiahui Chen, Han Xu, Tingting Liu, Ming Chen, Fang Yu, Yue Zhang

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引用次数: 0

Abstract

Menaquinone-7 (MK-7), a highly preferred form of vitamin K2, has garnered extensive attention due to its long half-life in the human body and numerous nutritional and pharmacological benefits. To establish a cost-effective microbial platform for MK-7 production, we engineered the eukaryotic model organism Saccharomyces cerevisiae. The complete biosynthesis pathway was modularized into three parts: the endogenous mevalonate (MVA) pathway, the endogenous shikimate (SA) pathway, and a heterologous menaquinone (MK) module. Eleven key genes from the MK module were introduced into the yeast chassis using selection markers for His, Leu, and Met, creating the engineered strain YK-1. We then optimized the fermentation medium and conditions, and the MK-7 titer reached 0.413 mg/L. This represents a 31.1% increase over the non-optimized yield, demonstrating the successful de novo synthesis of MK-7 from simple carbon sources in a eukaryotic cell factory. This work not only expands the repertoire of chassis cells for MK-7 production but also provides a valuable framework for engineering biosynthesis pathways for other isoprenoids.

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通过从头合成和发酵优化工程酿酒酵母生产甲基萘醌-7。

甲基萘醌-7 （MK-7）是一种非常受欢迎的维生素K2形式，由于其在人体内的半衰期长以及许多营养和药理益处而引起了广泛的关注。为了建立一个具有成本效益的生产MK-7的微生物平台，我们设计了真核模式生物酿酒酵母菌。完整的生物合成途径被模块化为三个部分：内源性甲羟戊酸（MVA）途径、内源性莽草酸（SA）途径和异源甲基萘醌（MK）模块。利用His、Leu和Met的选择标记，将MK模块中的11个关键基因导入酵母底盘，形成工程菌株YK-1。对发酵培养基和发酵条件进行优化，MK-7滴度达到0.413 mg/L。这比未优化的产率提高了31.1%，证明了在真核细胞工厂中从简单碳源成功地从头合成了MK-7。这项工作不仅扩大了MK-7生产的底盘细胞的曲目，而且为其他异戊二烯类化合物的工程生物合成途径提供了有价值的框架。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology Letters 工程技术-生物工程与应用微生物

CiteScore

5.90

自引率

3.70%

发文量

108

审稿时长

1.2 months

期刊介绍： Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them. All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included. Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields. The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories. Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.