Chemoenzymatic synthesis of trehalose analogues: Rapid access to chemical probes for investigating mycobacteria

Bailey L. Urbanek, Douglas C. Wing, Krystal S. Haislop, Chelsey J. Hamel, Rainer Kalscheuer, Peter J. Woodruff, Benjamin M. Swarts

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Trehalose analogues are emerging as valuable tools for investigating Mycobacterium tuberculosis, but progress in this area is slow due to the difficulty in synthesizing these compounds. Here, we report a chemoenzymatic synthesis of trehalose analogues that employs the heat-stable enzyme trehalose synthase (TreT) from the hyperthermophile Thermoproteus tenax. By using TreT, various trehalose analogues were prepared quickly (1 h) in high yield (up to >99 % by HPLC) in a single step from readily available glucose analogues. To demonstrate the utility of this method in mycobacteria research, we performed a simple "one-pot metabolic labeling" experiment that accomplished probe synthesis, metabolic labeling, and imaging of M. smegmatis in a single day with only TreT and commercially available materials. Trehalose tools for TB: A one-step chemoenzymatic method for the rapid and efficient synthesis of trehalose analogues was developed. This method enabled facile preparation and administration of a trehalose-based probe for detecting mycobacteria, which might enable the development of new diagnostic tools for tuberculosis (TB) research.

Original languageEnglish
Pages (from-to)2066-2070
Number of pages5
JournalChemBioChem
Volume16
Issue number17
DOIs
StatePublished - 2015

Keywords

  • chemoenzymatic synthesis
  • click chemistry
  • glycolipids
  • mycobacteria
  • trehalose

Fingerprint

Dive into the research topics of 'Chemoenzymatic synthesis of trehalose analogues: Rapid access to chemical probes for investigating mycobacteria'. Together they form a unique fingerprint.

Cite this