College of Enology, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
College of Enology, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
Biotechnol Adv. 2020 Nov 15;44:107628. doi: 10.1016/j.biotechadv.2020.107628. Epub 2020 Sep 1.
Limonene and its derivatives have great market potential with diverse applications in food, pharmaceuticals, cosmetics, etc. Commercial production of limonene and its derivatives through extraction from plants suffers from the unstable market supply, while chemical synthesis of these compounds is hindered by high energy consumption and pollutant emission. Microbial biosynthesis provides a promising alternative approach for the sustainable supply of limonene and its derivatives. However, low efficiency and specificity of the biosynthetic enzymes and pathways in heterologous hosts make it still challenging for the commercialization of microbial limonene production. On the other hand, the limonene toxicity heavily reduces cellular fitness, which poses a serious challenge for improving limonene titer. Here, we critically review the recent progresses in engineering microbes for limonene biosynthesis and derivation with the emphasis on enzyme characterization and pathway optimization. In particular, we introduce the current trends in microbial limonene decoration for the biosynthesis of bio-active molecules such as α-terpineol and perillyl alcohol. We also discuss the feasible strategies for relieving limonene toxicity and enhancing the robustness of microbial cell factories.
柠檬烯及其衍生物具有巨大的市场潜力，在食品、制药、化妆品等领域有广泛的应用。从植物中提取柠檬烯及其衍生物进行商业生产受到不稳定的市场供应的限制，而这些化合物的化学合成受到高能耗和污染物排放的阻碍。微生物生物合成为柠檬烯及其衍生物的可持续供应提供了一种有前途的替代方法。然而，异源宿主中生物合成酶和途径的效率和特异性较低，使得微生物柠檬烯生产的商业化仍然具有挑战性。另一方面，柠檬烯的毒性严重降低了细胞的适应性，这对提高柠檬烯的产量构成了严重挑战。在这里，我们批判性地回顾了用于柠檬烯生物合成和衍生的工程微生物的最新进展，重点介绍了酶的特性和途径的优化。特别是，我们介绍了微生物柠檬烯修饰用于生物活性分子如α-松油醇和紫苏醇生物合成的当前趋势。我们还讨论了缓解柠檬烯毒性和增强微生物细胞工厂鲁棒性的可行策略。
