角鲨烯 (C30H50) 是一种无环三萜化合物，以其多种生理功能而闻名，例如抗癌和抗氧化特性，使其在食品和制药领域具有无价的价值。由于自然资源的限制，微生物发酵已成为突出趋势。裂殖壶菌属 (Schizochytrium sp.) 已知拥有完整的甲羟戊酸 (MVA) 途径，具有生物合成角鲨烯的固有能力。然而，MVA 和角鲨烯合成途径中的关键基因及其修饰的相关启动子元件都缺乏报道。这项研究首先克隆并表征了源自转录组测序数据的 13 个内源启动子。随后，从上述库中选择了五个表现出不同表达强度的启动子，以促进在MVA途径中至关重要的角鲨烯合酶基因角鲨烯合成酶（SQS）的过度表达。最终，鉴定出一种转化菌株，命名为SQS-3626，其角鲨烯产量是野生型菌株的2.8倍。最后对发酵培养基中氮源浓度和微量元素含量进行优化。经过 120 小时的分批补料发酵后，转化菌株 SQS-3626 中角鲨烯的累积最终产量达到 2.2 g/L。© 2024 Wiley‐VCH GmbH。

Squalene (C30H50) is an acyclic triterpenoid compound renowned for its myriad physiological functions, such as anticancer and antioxidative properties, rendering it invaluable in both the food and pharmaceutical sectors. Due to the natural resource constraints, microbial fermentation has emerged as a prominent trend. Schizochytrium sp., known to harbor the intact mevalonate acid (MVA) pathway, possesses the inherent capability to biosynthesize squalene. However, there is a dearth of reported key genes in both the MVA and the squalene synthesis pathways, along with the associated promoter elements for their modification. This study commenced by cloning and characterizing 13 endogenous promoters derived from transcriptome sequencing data. Subsequently, five promoters exhibiting varying expression intensities were chosen from the aforementioned pool to facilitate the overexpression of the squalene synthase gene squalene synthetase (SQS), pivotal in the MVA pathway. Ultimately, a transformed strain designated as SQS-3626, exhibiting squalene production 2.8 times greater than that of the wild-type strain, was identified. Finally, the optimization of nitrogen source concentrations and trace element contents in the fermentation medium was conducted. Following 120 h of fed-batch fermentation, the accumulated final squalene yield in the transformed strain SQS-3626 reached 2.2 g/L.© 2024 Wiley‐VCH GmbH.