NRPS-like Gene LYS2 Contributed to the Biosynthesis of Cyclo(Pro-Val) in a Multistress-Tolerant Aromatic Probiotic, Meyerozyma guilliermondii GXDK6.

Autor: Bu R; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China., Li Z; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China., Qin Q; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China., Bai H; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China., Meng C; Guangxi Key Laboratory for Green Processing of Sugar Resources, Guangxi College Key Laboratory of Innovation Research on Medical and Engineering Integration, Liuzhou Key Laboratory of Guizhong Characteristic Medicinal Resources, Medical College, College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China., Wei R; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China., Chen X; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China., Wu S; Guangxi Key Laboratory for Green Processing of Sugar Resources, Guangxi College Key Laboratory of Innovation Research on Medical and Engineering Integration, Liuzhou Key Laboratory of Guizhong Characteristic Medicinal Resources, Medical College, College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China., Kashif M; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China.; Guangxi Key Laboratory for Green Processing of Sugar Resources, Guangxi College Key Laboratory of Innovation Research on Medical and Engineering Integration, Liuzhou Key Laboratory of Guizhong Characteristic Medicinal Resources, Medical College, College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China.; National Engineering Research Center for Non-Food Biorefinery, Guangxi Research Center for Biological Science and Technology, Guangxi Academy of Sciences, Nanning 530007, China., He S; Guangxi Birth Defects Prevention and Control Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530033, China., Jiang C; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China.; Guangxi Key Laboratory for Green Processing of Sugar Resources, Guangxi College Key Laboratory of Innovation Research on Medical and Engineering Integration, Liuzhou Key Laboratory of Guizhong Characteristic Medicinal Resources, Medical College, College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China.; National Engineering Research Center for Non-Food Biorefinery, Guangxi Research Center for Biological Science and Technology, Guangxi Academy of Sciences, Nanning 530007, China.
Jazyk: angličtina
Zdroj: Journal of agricultural and food chemistry [J Agric Food Chem] 2024 Dec 19. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1021/acs.jafc.4c08573
Abstrakt: Cyclo(Pro-Val) is a diketopiperazine (DKP) found widespread in marine microbes and resulting food products. With new bioactivities of cyclo(Pro-Val) being continually discovered, its potential applications in agriculture and food are becoming more evident, highlighting the need for efficient and practical methods to produce these compounds. However, the biosynthesis mechanisms of cyclo(Pro-Val), particularly in probiotics, remain unclear, and the functional identification of nonribosomal peptide synthases (NRPS) is still limited. This study presents a new efficient cyclo(Pro-Val) production system using the marine probiotic Meyerozyma guilliermondii ( M. guilliermondii ) GXDK6 as a chassis cell. We further characterized an NRPS-like gene, LYS2 , which spans 3825 bp and encodes an l-2-amino-hexanedioic acid reductase (Lys2p) consisting of 1274 amino acids. A novel macrocyclization mechanism was revealed involving the peptide N-terminal and C-terminal imines mediated by Lys2p through nucleophilic reactions. Overexpressing LYS2 in GXDK6 resulted in a 45.5% increase in cyclo(Pro-Val) production, while knockout LYS2 completely halted its synthesis. This study revealed a novel metabolic regulatory pathway and biosynthetic mechanism for cyclo(Pro-Val) in marine yeast M. guilliermondii GXDK6. Refactoring the biosynthetic pathway in yeast through LYS2 provides an alternative approach for producing cyclo(Pro-Val).
Databáze: MEDLINE