Mechanistic insights into 1‐deoxy‐<scp>d</scp>‐xylulose 5‐phosphate reductoisomerase, a key enzyme of the <scp>MEP</scp> terpenoid biosynthetic pathway

Li, Heng; Tian, Jianmin; Sun, Wei; Qin, Wei

doi:10.1111/febs.12516

Cited by 16 publications

(13 citation statements)

References 42 publications

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“…DXP was synthesized according to a procedure previously reported27. The preparation of E. coli DXR was carried out in accordance with a published method28. HPLC grade methanol was purchased from Sigma-Aldrich Chemical Co. (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial mechanism of theaflavins: They target 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway

Xian

Qiao

Zhang

et al. 2016

Sci Rep

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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 (IC50 162.1 μM) and theaflavin-3,3′-digallate exhibiting the highest (IC50 14.9 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.

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Section: Methodsmentioning

confidence: 99%

Antimicrobial mechanism of theaflavins: They target 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway

Xian

Qiao

Zhang

et al. 2016

Sci Rep

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“…DXP was synthesized according to a procedure previously reported [20]. The preparation of E. coli DXR was carried out in accordance with a published method [21]. Deaerated water was prepared by boiling Minipore water for 30 min, cooled to room temperature and then bubbled with a gentle N2 flow for 6 hours.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of green tea and the catechins against 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway

et al. 2016

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1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) is the first committed enzyme in the MEP terpenoid biosynthetic pathway and also a validated antimicrobial target. Green tea which is rich in polyphenolic components such as the catechins, possesses a plenty of pharmacological activities, in particular an antibacterial effect. To uncover the antibacterial mechanism of green tea and to seek new DXR inhibitors from natural sources, the DXR inhibitory activity of green tea and its main antimicrobial catechins were investigated in this study. The results show that the raw extract of green tea and its ethyl acetate fraction are able to suppress DXR activity explicitly. Further determination of the DXR inhibitory capacity of eight catechin compounds demonstrates that the most active compound is gallocatechin gallate that is able to inhibit around 50% activity of DXR at 25μM. Based on these data, the primary structure-activity relationship of the catechins against DXR is discussed. This study would be very helpful to elucidate the antimicrobial mechanism of green tea and the catechins and also would be very useful to direct the rational utilization of them as food additives.

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“…General: Plasmid pFMH30 for the synthesis of recombinant DXS of Rhodobacter capsulatus was a kind gift from Prof. C. Dale Poulter, Chemistry Department, University of Utah. The bacterial strain E. coli BL21 (DE3) was from the stock of our institute, and the plasmid pET15b-DXR was constructed in our preliminary work [8]. DEAE Sephadex A-25 was from Sigma, Ni-NTA Agarose resin from Qiagen, sodium pyruvate, ThPP and NADPH from Sangon Biotech, and D-GAP was from our preliminary work [5].…”

Section: Methodsmentioning

confidence: 99%

A Specific Process to Purify 2-Methyl-D-Erythritol-4-Phosphate Enzymatically Converted from D-Glyceraldehyde-3-Phosphate and Pyruvate

Yang

Deng

et al. 2015

Natural Product Communications

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A one-pot enzymatic cascade was established to synthesize MEP, one of the key intermediates in the MEP terpenoid biosynthetic pathway. D-GAP and sodium pyruvate were converted to MEP in a reaction catalyzed by DXP synthase and DXP reductoisomerase (DXR) in the presence of the coenzymes ThPP, NADPH, and Mg 2+. The product was then isolated by using a specific two-step purification process and MEP was obtained in a yield of nearly 60% and high purity. Importantly, MEP prepared by this way was totally free from contamination by minor amounts of DXP that was not completely convertible by DXR.

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Mechanistic insights into 1‐deoxy‐d‐xylulose 5‐phosphate reductoisomerase, a key enzyme of the MEP terpenoid biosynthetic pathway

Cited by 16 publications

References 42 publications

Antimicrobial mechanism of theaflavins: They target 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway

Antimicrobial mechanism of theaflavins: They target 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway

Inhibition of green tea and the catechins against 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway

A Specific Process to Purify 2-Methyl-D-Erythritol-4-Phosphate Enzymatically Converted from D-Glyceraldehyde-3-Phosphate and Pyruvate

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