Chemoenzymatic syntheses of water-soluble lipid i fluorescent probes This Letter is dedicated to the memory of Professor Harry H. Wasserman, an inspirational scientist

Katsuhiko Mitachi, Shajila Siricilla, Lada Klaić, William M. Clemons, Michio Kurosu

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 (2Z,6E)-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.

Original languageEnglish (US)
Pages (from-to)3441-3446
Number of pages6
JournalTetrahedron Letters
Volume56
Issue number23
DOIs
StatePublished - May 25 2015

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Fluorescent Dyes
Peptidoglycan
Lipids
Data storage equipment
Water
Phosphates
Enzymes
Biosynthesis
Membranes
Solubility
Reaction Time
Escherichia coli
lipid I
Bacteria
Pharmaceutical Preparations
Substrates
prenyl

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Chemoenzymatic syntheses of water-soluble lipid i fluorescent probes This Letter is dedicated to the memory of Professor Harry H. Wasserman, an inspirational scientist. / Mitachi, Katsuhiko; Siricilla, Shajila; Klaić, Lada; Clemons, William M.; Kurosu, Michio.

In: Tetrahedron Letters, Vol. 56, No. 23, 25.05.2015, p. 3441-3446.

Research output: Contribution to journalArticle

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