微生物源甲硫氨酸γ-裂解酶的研究进展

Research progress of methionine γ-lyase from microorganism

摘要:

甲硫氨酸γ-裂解酶（methionine γ-lyase，MGL）催化甲硫氨酸γ位C-S键的裂解反应，生成等摩尔的α-酮丁酸、甲基硫醇和氨。MGL降低胞内甲硫氨酸浓度，显著抑制恶性肿瘤细胞的生长和迁移，激发正常细胞的抗氧化反应，开发高效的MGL已成为肿瘤治疗和抗衰老研究的热点。MGL广泛存在于微生物中，而在哺乳动物中不存在，MGL是开发抗致病微生物感染药物的重要靶标。产物甲基硫醇及其衍生物是构成食品香味的主体成分，其组分和浓度决定了食品整体香味的形成，系统阐明MGL的催化机制和活性调节机制将推动食品品质及其稳定性的精准控制。本文总结了微生物源MGL的挖掘、催化机制和改造方面的最新进展，讨论了MGL在癌症治疗、抗衰老、抗致病微生物感染以及食品香味合成和制造领域的应用情况，展望了MGL的发展前景与挑战。

关键词:甲硫氨酸γ-裂解酶;肿瘤治疗;抗衰老;抗感染;食品香味

Abstract:

Methionine γ-lyase (MGL) catalyzes the cleavage of C-S bond in methionine, which produces equimolar products including α-ketobutyric acid, methanethiol and ammonia. MGL reduces the intracellular concentration of methionine, which significantly inhibits the growth and migration of malignant tumor cells and triggers the antioxidant response in normal cells. Engineering MGL for enhancing its catalytic efficiency is the focus for tumor therapy and anti-aging. MGL widely exists in microorganisms, but not in mammals. MGL is an important target for the development of antimicrobial drugs toward microbial pathogens. Methanethiol and its derivatives are the main components of food aroma, and the composition and concentration of methanethiol and its derivatives determine the formation of food aroma. Elucidating the catalytic mechanism and identifying the key elements control the activity of MGL will promote the precise control of food quality and its stability. In this paper, the latest advances in the discovery, catalytic mechanism and engineering of MGL from microorganisms were summarized. The applications of MGL in tumor therapy, anti-aging, anti-microbial infection and synthesis and manufacturing of food aroma were discussed, and then the development and challenge of MGL were prospected.

Key words:methionine γ-lyase;tumor therapy;anti-aging;anti-microbial infection;food aroma