Chemo-enzymatic hybrid process for production of monatin, a high intensity sweetener

Conference Dates

September 24-28, 2017


Monatin, 4-hydroxy-4-(3-indolylmethyl)-glutamic acid, is a naturally occurring sweet amino acid isolated from the plant Sclerochiton ilicifolius, found in South Africa [1]. Monatin has two asymmetric centers at C2 and C4, the (2R,4R)-monatin isomer has been found to be the sweetest among its four stereoisomers. It is 2700 times sweeter than sugar and has a clean taste like sugar. Because of these properties, (2R,4R)-monatin has been expected as an new high-intensity sweetener [2]. However, industrial production process of (2R,4R)-monatin using inexpensive raw materials has not been established owing to the difficulty for optically specific synthesis. Here, we report a chemo-enzymatic hybrid process for production of (2R,4R)-monatin from l-tryptophan. In the steps of enzymatic reaction from l-tryptophan, l-amino acid deaminase and aldolase were used for production of 4-(Indole-3-ylmethyl)-4-hydroxy-2-oxoglutaric acid (IHOG) with pyruvic acid as co-substrate. The keto-form of (2R,4R)-monatin, (R)-IHOG, was specifically synthesized by using R-specific aldolase from Shingomonas sp. in the second reaction. In the next chemical reaction steps, (R)-IHOG was converted to the oxime form, reduced to (2R,4R) and (2S,4R)-monatin, and (2R,4R)-monatin salt was obtained from optical resolution by crystallization. By the combination of epimerization and crystallization, (2R,4R)-monatin was obtained specifically from the mixture of diastereomers. In this study, we established an efficient production process for (2R,4R)-monatin using both chemical and enzymatic reactions, and a large amount of (2R,4R)-monatin was prepared by the bench-scale production.

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