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

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. Please click Additional Files below to see the full abstract

Depression in Family Caregivers of the Frail Elderly in Sapporo, Japan : A Cross-Sectional Study

Background: Depression affecting caregivers is a risk factor for discontinuing at-home care. Objective: The present cross-sectional study was conducted to evaluate factors related to depression of family caregivers. Methods: A cross-sectional study was conducted in order to evaluate factors related to depression among family aregivers for the frail elderly with periodic nurse service in 2008, in 7 home-visiting nursing service stations in Sapporo, Japan. Caregivers were asked to answer a self-administered questionnaire about various factors that might affect their depression, and also to complete a Center for Epidemiologic Studies Depression Scale Evaluation (CES-D). We analyzed 71 pairs in total. Results: Factors related to poor health (OR=3.40, 95%CI: 1.13, 10.18) and a longer time spent physically caregiving (OR=3.08, 95%CI: 1.02, 9.35) were associated with being depressed. On the other hand, factors related to a good or fair economic position (OR=0.30, 95%CI: 0.10, 0.91), having a sister or brother who could help from the outside (OR=0.21, 95%CI: 0.05, 0.91), being able to relieve irritation caused by caregiving (OR=0.10, 95%CI: 0.03, 0.36), using the care service at home well (OR=0.24, 95%CI: 0.06, 0.98), and being able to pay more than 10,000 Japanese Yen by themselves as part of the total care service costs (OR=0.15, 95%CI: 0.04, 0.57) were associated with not being depressed. Conclusion: Caregivers should be supported not only informally but also by a new government funded system