| Structural highlights
Function
74AC1_SIRGR Catalyzes the transfer of a glucose moiety to the C-3 hydroxyl of mogrol to form mogroside IE (PubMed:25759326, Ref.3). Besides mogrol, UGT74AC1 also shows activity in vitro with quercetin and naringenin as substrate (PubMed:25759326).[1] [2]
Publication Abstract from PubMed
The addition of the O-linked N-acetylglucosamine (O-GlcNAc) is a significant modification for active molecules, such as proteins, carbohydrates, and natural products. However, the synthesis of terpenoid glycoside derivatives decorated with GlcNAc remains a challenging task due to the absence of glycosyltransferases, key enzymes for catalyzing the transfer of GlcNAc to terpenoids. In this study, we demonstrated that the enzyme mutant UGT74AC1(T79Y/L48M/R28H/L109I/S15A/M76L/H47R) efficiently transferred GlcNAc from uridine diphosphate (UDP)-GlcNAc to a variety of terpenoids. This powerful enzyme was employed to synthesize GlcNAc-decorated derivatives of terpenoids, including mogrol, steviol, andrographolide, protopanaxadiol, glycyrrhetinic acid, ursolic acid, and betulinic acid for the first time. To unravel the mechanism of UDP-GlcNAc recognition, we determined the X-ray crystal structure of the inactivated mutant UGT74AC1(His18A/Asp111A) in complex with UDP-GlcNAc at a resolution of 1.66 A. Through molecular dynamic simulation and activity analysis, we revealed the molecular mechanism and catalytically important amino acids directly involved in the recognition of UDP-GlcNAc. Overall, this study not only provided a potent biocatalyst capable of glycodiversifying natural products but also elucidated the structural basis for UDP-GlcNAc recognition by glycosyltransferases.
Enzymatic Synthesis of Novel Terpenoid Glycoside Derivatives Decorated with N-Acetylglucosamine Catalyzed by UGT74AC1.,Li J, Li R, Shang N, Men Y, Cai Y, Zeng Y, Liu W, Yang J, Sun Y J Agric Food Chem. 2024 Jun 26;72(25):14255-14263. doi: 10.1021/acs.jafc.4c02832. , Epub 2024 Jun 12. PMID:38867497[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dai L, Liu C, Zhu Y, Zhang J, Men Y, Zeng Y, Sun Y. Functional Characterization of Cucurbitadienol Synthase and Triterpene Glycosyltransferase Involved in Biosynthesis of Mogrosides from Siraitia grosvenorii. Plant Cell Physiol. 2015 Jun;56(6):1172-82. PMID:25759326 doi:10.1093/pcp/pcv043
- ↑ Dai L, Liu C, Zhu Y, Zhang J, Men Y, Zeng Y, Sun Y. Functional Characterization of Cucurbitadienol Synthase and Triterpene Glycosyltransferase Involved in Biosynthesis of Mogrosides from Siraitia grosvenorii. Plant Cell Physiol. 2015 Jun;56(6):1172-82. PMID:25759326 doi:10.1093/pcp/pcv043
- ↑ Li J, Li R, Shang N, Men Y, Cai Y, Zeng Y, Liu W, Yang J, Sun Y. Enzymatic Synthesis of Novel Terpenoid Glycoside Derivatives Decorated with N-Acetylglucosamine Catalyzed by UGT74AC1. J Agric Food Chem. 2024 Jun 26;72(25):14255-14263. PMID:38867497 doi:10.1021/acs.jafc.4c02832
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