title: Antimicrobial mechanism of theaflavins: They target 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway.
abstract: 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is the first committed enzyme in the 2-methyl-D-erythritol 4-phosphate (MEP) terpenoid biosynthetic pathway and is also a validated antimicrobial target. Theaflavins, which are polyphenolic compounds isolated from fermented tea, possess a wide range of pharmacological activities, especially an antibacterial effect, but little has been reported on their modes of antimicrobial action. To uncover the antibacterial mechanism of theaflavins and to seek new DXR inhibitors from natural sources, the DXR inhibitory activity of theaflavins were investigated in this study. The results show that all four theaflavin compounds could specifically suppress the activity of DXR, with theaflavin displaying the lowest effect against DXR (IC50162.1 μM) and theaflavin-3,3'-digallate exhibiting the highest (IC5014.9 μM). Moreover, determination of inhibition kinetics of the theaflavins demonstrates that they are non-competitive inhibitors of DXR against 1-deoxy-D-xylulose 5-phosphate (DXP) and un-competitive inhibitors with respect to NADPH. The possible interactions between DXR and the theaflavins were simulated via docking experiments.
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Hui
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Yue
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
authors.forename: Wen-Yun
authors.initials: WY
authors.lastname: Gao
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D004896:Erythritol / Q000031:analogs & derivatives / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects*; D062105:Molecular Docking Simulation; D010316:Particle Size; D013729:Terpenes / Q000378:metabolism
chemical_list: C000598497:2-methyl-D-erythritol-4-phosphate; D000900:Anti-Bacterial Agents; D044946:Biflavonoids; D013729:Terpenes; C056068:theaflavin; D002392:Catechin; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D000469:Alkaline Phosphatase; D019747:Aldose-Ketose Isomerases; D004896:Erythritol