Chemoenzymatic syntheses of water-soluble lipid I fluorescent probes. Issue 23 (3rd June 2015)

• Record Type: Journal Article
• Authors: Mitachi, Katsuhiko; Siricilla, Shajila; Klaić, Lada; Clemons, William M.; Kurosu, Michio
• Is Part Of: Tetrahedron letters. Volume 56:Issue 23(2015)
• Page Start: 3441
• Page End: 3446
• Publication Date: 2015-06-03
• Subjects: Translocase I (MraY/MurX) -- MurG -- Lipid I -- Lipid II -- Chemoenzymatic synthesis; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2015.01.044
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Abstract: 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 C50 - or C55 -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 (2 Z, 6 E )-farnesyl phosphate (C15 -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.