Zheng Xiaochun, Liu Yijuan, Li Yajun, Wang Yanan, Yang Xiaobing
College of Enology, Northwest A&F University, Yangling, Shaanxi 712100, China.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
J Agric Food Chem. 2024 Dec 4;72(48):26777-26785. doi: 10.1021/acs.jafc.4c07705. Epub 2024 Nov 6.
Microbial production offers a sustainable route to plant- and chemical-based manufacturing. 2-Phenylethanol (2-PE) has been widely used in foods, flavors, and pharmaceuticals. Herein, biosynthesis of 2-PE was achieved for the first time by rewiring the non-native producer . Our results showed that the generation of phenylalanine (Phe) and the recycling of the amino group could be bypassed since the Ehrlich pathway outperformed the phenylacetaldehyde-dependent one in biosynthesis of 2-PE when the adenosine 5'-triphosphate (ATP) citrate synthase (ACL) was inactivated. The 2-PE titer was enhanced to 151.7 mg/L in a shake flask by alleviating feedback inhibition, enhancing precursor availability and cofactor balance. Finally, the production of 2-PE was elevated to 1.06 g/L with a yield of 8.5 mg/g glucose and productivity of 8 mg/L/h in a 3 L bioreactor. Our results should shed light on the microbial production of other aromatic derivatives with .
微生物生产为基于植物和化学的制造提供了一条可持续的途径。2-苯乙醇（2-PE）已广泛应用于食品、香料和制药领域。在此，通过改造非天然生产菌株首次实现了2-PE的生物合成。我们的结果表明，当腺苷5'-三磷酸（ATP）柠檬酸合酶（ACL）失活时，由于埃利希途径在2-PE生物合成中优于苯乙醛依赖途径，因此可以绕过苯丙氨酸（Phe）的生成和氨基的循环利用。通过减轻反馈抑制、提高前体可用性和辅因子平衡，摇瓶中2-PE的滴度提高到了151.7 mg/L。最终，在3 L生物反应器中，2-PE的产量提高到了1.06 g/L，葡萄糖产率为8.5 mg/g，生产率为8 mg/L/h。我们的结果应为其他芳香族衍生物的微生物生产提供启示。
