Chemoenzymatic syntheses of water-soluble lipid I fluorescent probes

TETRAHEDRON LETTERS

卷:56

Article

Mitachi, Katsuhiko¹  Siricilla, Shajila¹  Klaic, Lada²  Clemons, William M., Jr.²  Kurosu, Michio¹ 

[1] Univ Tennessee, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA

[2] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA

关键词: Translocase I (MraY/MurX);    MurG;    Lipid I;    Lipid II;    Chemoenzymatic synthesis;   

DOI  :  10.1016/j.tetlet.2015.01.044

来源: Elsevier

【 摘 要 】

Peptidoglycan (PG) is unique to bacteria, and thus, the enzymes responsible for its biosynthesis are promising antibacterial drug targets. The membrane-embedded enzymes in PG remain significant challenges in studying their mechanisms due to the fact that preparations of suitable enzymatic substrates require time-consuming biological transformations or chemical synthesis. Lipid I (MurNAc(pentapeptide)pyrophosphoryl prenol) is an important PG biosynthesis intermediate to study the central enzymes, translocase I (MraY/MurX) and MurG. Lipid I isolated from nature contains the C-50- or C-55-prenyl unit that shows extremely poor water-solubility that renders studies of translocase I and MurG enzymes difficult. We have studied biological transformation of water soluble lipid I fluorescent probes using bacterial membrane fractions and purified MraY enzymes. In our investigation of the minimum structural requirements of the prenyl phosphates in MraY-catalyzed lipid I synthesis, we found that (2Z,6E)-famesyl phosphate (C-15-phosphate) can be recognized by Escherichia coli MraY to generate the water-soluble lipid I fluorescent probe in high-yields. Under the optimized conditions, the same reaction was performed by using the purified MraY from Hydrogenivirga spp. to afford the lipid I analog with high-yields in a short reaction time. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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