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Enzyme Microb Technol. 2014 Oct;64-65:38-43. doi: 10.1016/j.enzmictec.2014.07.001. Epub 2014 Jul 11.

Production of rubusoside from stevioside by using a thermostable lactase from Thermus thermophilus and solubility enhancement of liquiritin and teniposide.

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Institutes of Green Bio Science & Technology, Seoul National University, Gangwon-do 232-916, Republic of Korea.
Korea Atomic Energy Research Institute Advanced Radiation Technology Institute, Jeollabuk-do 500-185, Republic of Korea.
Research Center for Proteinaceous Materials (RCPM), Chosun University, Gwang-Ju 501-759, Republic of Korea.
Infection Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeollabuk-do 580-185, Republic of Korea.
Audubon Sugar Institute, Louisiana State University Agricultural Center, Gabriel, LA 70776, USA.
Department of Food Science and Nutrition, Dankook University, Gyeonggi-do 448-701, Republic of Korea.
Institutes of Green Bio Science & Technology, Seoul National University, Gangwon-do 232-916, Republic of Korea; Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea. Electronic address:


Solubility is an important factor for achieving the desired plasma level of drug for pharmacological response. About 40% of drugs are not soluble in water in practice and therefore are slowly absorbed, which results in insufficient and uneven bioavailability and GI toxicity. Rubusoside (Ru) is a sweetener component in herbal tea and was discovered to enhance the solubility of a number of pharmaceutically and medicinally important compounds, including anticancer compounds. In this study, thirty-one hydrolyzing enzymes were screened for the conversion of stevioside (Ste) to Ru. Recombinant lactase from Thermus thermophiles which was expressed in Escherichia coli converted stevioside to rubusoside as a main product. Immobilized lactase was prepared and used for the production of rubusoside; twelve reaction cycles were repeated with 95.4% of Ste hydrolysis and 49 g L(-1) of Ru was produced. The optimum rubusoside synthesis yield was 86% at 200 g L(-1), 1200 U lactase. The purified 10% rubusoside solution showed increased water solubility of liquiritin from 0.98 mg mL(-1) to 4.70±0.12 mg mL(-1) and 0 mg mL(-1) to 3.42±0.11 mg mL(-1) in the case of teniposide.


Immobilized lactase; Liquiritin; Rubusoside; Teniposide; Thermus thermophilus

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