Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Pharmaceutical Biology Research Group, School of Pharmacy, Institut Teknologi Bandung, 40132 Bandung, Indonesia.
J Agric Food Chem. 2020 Apr 15;68(15):4447-4455. doi: 10.1021/acs.jafc.0c00375. Epub 2020 Apr 3.
Squalene synthase (SQS) catalyzes the conversion of two farnesyl pyrophosphates to squalene, an important intermediate in between isoprene and valuable triterpenoids. In this study, we have constructed a novel biosynthesis pathway for squalene in and performed metabolic engineering aiming at facilitating further exploitation and production of squalene-derived triterpenoids. Therefore, systematic studies and analysis were performed including selection of multiple SQS candidates from various organisms, comparison of expression vectors, optimization of cultivation temperatures, and examination of rate-limiting factors within the synthetic pathway. We were, for the first time, able to obtain squalene synthesis in . Furthermore, we achieved a 29-fold increase of squalene yield (0.26-7.5 mg/L) by expressing SQS from and eliminating bottlenecks within the upstream methylerythritol-phosphate pathway. Moreover, our findings showed that also could positively affect the production of squalene.
鲨烯合酶（SQS）催化两分子法呢基焦磷酸转化为鲨烯，鲨烯是异戊二烯和有价值的三萜类化合物之间的重要中间体。在这项研究中，我们构建了 中鲨烯的新型生物合成途径，并进行了代谢工程，旨在促进鲨烯衍生三萜类化合物的进一步开发和生产。因此，我们进行了系统的研究和分析，包括从各种生物体中选择多个 SQS 候选物、比较表达载体、优化培养温度以及检查合成途径中的限速因素。我们首次在 中获得了鲨烯的合成。此外，通过表达来自 的 SQS 并消除上游甲羟戊酸途径中的瓶颈，我们将鲨烯的产量提高了 29 倍（0.26-7.5mg/L）。此外，我们的研究结果表明，也可以正向影响鲨烯的生产。
