title: Production of rubusoside from stevioside by using a thermostable lactase from Thermus thermophilus and solubility enhancement of liquiritin and teniposide.
abstract: 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.
authors.affiliation: Institutes of Green Bio Science & Technology, Seoul National University, Gangwon-do 232-916, Republic of Korea.
authors.forename: Thi Thanh Hanh
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Korea Atomic Energy Research Institute Advanced Radiation Technology Institute, Jeollabuk-do 500-185, Republic of Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Jung
authors.affiliation: Research Center for Proteinaceous Materials (RCPM), Chosun University, Gwang-Ju 501-759, Republic of Korea.
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
authors.affiliation: Infection Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeollabuk-do 580-185, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Audubon Sugar Institute, Louisiana State University Agricultural Center, Gabriel, LA 70776, USA.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Moon
authors.affiliation: Department of Food Science and Nutrition, Dankook University, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Misook
authors.initials: M
authors.lastname: Kim
authors.affiliation: 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: kimdm@snu.ac.kr.
authors.forename: Doman
authors.initials: D
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001682:Biological Availability; D045786:Diterpenes, Kaurane / Q000096:biosynthesis* / Q000378:metabolism* / Q000494:pharmacology; D004795:Enzyme Stability; D004800:Enzymes, Immobilized / Q000235:genetics / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000493:pharmacokinetics; D005960:Glucosides / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007218:Industrial Microbiology; D043322:Lactase / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D013549:Sweetening Agents / Q000378:metabolism / Q000494:pharmacology; D013696:Temperature; D013713:Teniposide / Q000737:chemistry / Q000493:pharmacokinetics; D016963:Thermus thermophilus / Q000201:enzymology* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D045786:Diterpenes, Kaurane; D004800:Enzymes, Immobilized; D044950:Flavanones; D005960:Glucosides; D011994:Recombinant Proteins; D013549:Sweetening Agents; C012043:stevioside; D013713:Teniposide; D043322:Lactase; C512196:liquiritin; C056177:rubusoside
keywords: Immobilized lactase; Liquiritin; Rubusoside; Teniposide; Thermus thermophilus