Applied Environmental Biology Laboratory, Graduate School of Pharmaceutical Sciences, Osaka University.
School of Pharmaceutical Sciences, Wakayama Medical University.
Biol Pharm Bull. 2022;45(8):1191-1197. doi: 10.1248/bpb.b22-00316.
Gamma-glutamylcysteine (γ-EC) is an intermediate generated in the de novo synthesis of glutathione (GSH). Recent studies have revealed that the administration of γ-EC shows neuroprotective effects against oxidative stress in age-related disorders and chronic diseases like Alzhiemer's disease in model animals, which is not expected function in GSH. A phytochelatin synthase-like enzyme derived from Nostoc sp. (NsPCS) mediates γ-EC synthesis from GSH. To achieve low-cost and stable commercial level supply, the availability of immobilized NsPCS for γ-EC production was investigated in this study. Among the tested immobilization techniques, covalent binding to the cellulose carrier was most effective, and could convert GSH completely to γ-EC without decreasing the yield. The stable conversion of γ-EC from 100 mM GSH was achieved by both batch repeated and continuous reactions using the immobilized NsPCS on cellulose sheet and column shape monolith, respectively. The immobilization of NsPCS on those carriers is promising alternative technique for high-yielding and cost-effective production of γ-EC on its commercial applications.
γ-谷氨酰半胱氨酸（γ-EC）是谷胱甘肽（GSH）从头合成过程中的一种中间产物。最近的研究表明，在模型动物的与年龄相关的疾病和慢性疾病（如阿尔茨海默病）中，γ-EC 的给药显示出对氧化应激的神经保护作用，这在 GSH 中是没有预期功能的。一种来自念珠藻属（Nostoc sp.）的植物螯合肽合酶样酶（NsPCS）介导 GSH 合成 γ-EC。为了实现低成本和稳定的商业水平供应，本研究考察了固定化 NsPCS 用于 γ-EC 生产的可用性。在测试的固定化技术中，与纤维素载体的共价结合最为有效，并且可以将 GSH 完全转化为 γ-EC，而不会降低产率。使用纤维素片和柱状整体式上固定化的 NsPCS，通过分批重复和连续反应分别实现了从 100mM GSH 到 γ-EC 的稳定转化。NsPCS 在这些载体上的固定化是在其商业应用中实现高产和高性价比γ-EC 生产的有前途的替代技术。
