title: Synthesis of umbelliferone derivatives inEscherichia coliand their biological activities.
abstract: BACKGROUND
  Umbelliferone, also known as 7-hydroxycoumarin, is a phenolic metabolite found in many familiar plants. Its derivatives have been shown to have various pharmacological and chemo-preventive effects on human health. A uridine diphosphate glycosyltransferase YjiC fromBacillus licheniformisDSM 13, a cytochrome P450BM3 (CYP450 BM3) variant namely mutant 13 (M13) fromBacillus megaterium, and anO-methyltransferase fromStreptomyces avermitilis(SaOMT2) were used for modifications of umbelliferone.
  
  
  RESULTS
  Three umbelliferone derivatives (esculetin, skimmin, and herniarin) were generated through enzymatic and whole cell catalysis. To improve the efficiencies of biotransformation, different media, incubation time and concentration of substrate were optimized and the production was scaled up using a 3-L fermentor. The maximum yields of esculetin, skimmin, and herniarin were 337.10 μM (67.62%), 995.43 μM (99.54%), and 37.13 μM (37.13%), respectively. The water solubility of esculetin and skimmin were 1.28-folds and 3.98-folds as high as umbelliferone, respectively, whereas herniarin was 1.89-folds less soluble than umbelliferone. Moreover, the antibacterial and anticancer activities of herniarin showed higher than umbelliferone, esculetin and skimmin.
  
  
  CONCLUSIONS
  This study proves that both native and engineered enzymes could be employed for the production of precious compounds via whole cell biocatalysis. We successfully produced three molecules herniarin, esculetin and skimmin in practical amounts and their antibacterial and anticancer properties were accessed. One of the newly synthesized molecules the present research suggests that the combinatorial biosynthesis of different biosynthetic enzymes could rapidly promote to a novel secondary metabolite.
authors.affiliation: Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.
authors.forename: Luan Luong
authors.initials: LL
authors.lastname: Chu
authors.affiliation: Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.|Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.
authors.forename: Ramesh Prasad
authors.initials: RP
authors.lastname: Pandey
authors.affiliation: Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.
authors.forename: Haet Nim
authors.initials: HN
authors.lastname: Lim
authors.affiliation: Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.|Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Center for Molecular Biology, Institute of Research and Development, Duy Tan University, K7/25 Quang Trung, Danang, Vietnam.
authors.forename: Nguyen Huy
authors.initials: NH
authors.lastname: Thuan
authors.affiliation: Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.
authors.forename: Tae-Su
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Life Science and Biochemical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.|Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460 Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
keywords: Glycosylation; Hydroxylation; Methylation; Umbelliferone