Glycyrrhetic Acid 3‐O‐Mono‐β‐d‐glucuronide (GAMG): An Innovative High‐Potency Sweetener with Improved Biological Activities

Abstract

Glycyrrhetic acid 3-O-mono-β-d-glucuronide (GAMG) is an important derivative of glycyrrhizin (GL) and has attracted considerable attention, especially in the food and pharmaceutical industries, due to its natural high sweetness and strong biological activities. The biotransformation process is becoming an efficient route for GAMG production with the advantages of mild reaction conditions, environmentally friendly process, and high production efficiency. Recent studies showed that several β-glucuronidases (β-GUS) are key GAMG-producing enzymes, displaying a high potential to convert GL directly into the more valuable GAMG and providing new insights into the generation of high-value compounds. This review provides details of the structural properties, health benefits, and potential applications of GAMG. The progress in the development of the biotransformation processes and fermentation strategies to improve the yield of GAMG is also discussed. This work further summarizes recent advances in the enzymatic synthesis of GAMG using β-GUS with emphasis on the physicochemical and biological properties, molecular modifications, and enzymatic strategies to improve β-GUS biocatalytic efficiencies. This information contributes to a better framework to explore production and application of bioactive GAMG.

Enzymatic Synthesis of Novel Glycyrrhizic Acid Glucosides Using a Promiscuous Bacillus Glycosyltransferase

“…Sugar moieties appended to natural products not only enhance their solubility but also influence their pharmacological efficacies and/or molecular mechanisms of action [40]. GL as the most representative glycosylated product of GA has been clinically used as a hepatoprotective medicine for the treatment of chronic hepatitis, liver cirrhosis and hepatic carcinoma [12].…”

Bioavailability Based on the Gut Microbiota: a New Perspective

“…GL is not easily absorbed from the intestine into the blood when administered orally to humans, as the structure, consisting of two glucuronide molecules, is strongly polar (94). However, one distal glucuronic acid of GL can be hydrolyzed by ␤-Dglucuronidase (␤-GUS) derived from intestinal bacteria and then converted to GAMG, which exhibits moderate membrane permeability with suitable molecular polarity, possibly because of the sugar conjugation in this molecule, leading to an elevation in bioavailability (95,96). Gut bacteria, including Eubacterium sp.…”

De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae

“…GAMG is composed of one molecule of GA as aglycone and one molecule of glucuronic acid (GlcA) ( Figure 1A ). GAMG has been shown to have similar pharmacological effects as GA and GL ( Guo et al, 2018 ). GAMG can also be used as a natural innovative sweetener with health effects in food industry, because it is 5- and 941-times sweeter than GL and sucrose, respectively.…”

“…Moreover, GAMG is a promising emulsifier or solubilization agent in various kinds of cosmetic products. Considering the great importance and the expanded market of GAMG as a valuable drug, potent food additives, and solubilization agent ( Guo et al, 2018 ), an efficient strategy to synthesize GAMG is highly demanded for large-scale production of GAMG in industry.…”

“…The extremely low GAMG content in licorice reduces the efficiency of GAMG extraction (<0.1 mg/g) ( Song et al, 2017 ), and wild licorice overharvesting results in environmental damage and even desertification. Chemical synthesis of GAMG suffers from complicated process, high cost, and environmental pollution ( Guo et al, 2018 ). Recently, GAMG and lignocellulosic enzyme were produced by the licorice straw as a medium for via solid-state fermentation (SSF) of endophytic fungus Chaetomium globosum DX-THS3( Gao et al, 2021 ), however the 90% GL transformed to GAMG needs 15 days.…”