Indolyl septanoside synthesis for in vivo screening of bacterial septanoside hydrolases

Aditya R. Pote, Sergi Pascual, Antoni Planas, Mark W. Peczuh

Research output: Indexed journal article Articlepeer-review

2 Citations (Scopus)

Abstract

Building-up and breaking-down of carbohydrates are processes common to all forms of life. Glycoside hydrolases are a broad class of enzymes that play a central role in the cleavage of glycosidic bonds, which is fundamental to carbohydrate degradation. The large majority of substrates are five-and six-membered ring glycosides. Our interest in seven-membered ring septanose sugars has inspired the development of a way to search for septanoside hydrolase activity. Described here is a strategy for the discovery of septanoside hydrolases that uses synthetic indolyl septanosides as chromogenic substrates. Access to these tool compounds was enabled by a route where septanosyl halides act as glycosyl donors for the synthesis of the indolyl septanosides. The screening strategy leverages the known dimerization of 3-hydroxy-indoles to make colored dyes, as occurs when the β-galactosidase substrate X-Gal is hydrolyzed. Because screens in bacterial cells would enable searches in organisms that utilize heptoses or from metagenomics libraries, we also demonstrate that septanosides are capable of entering E. coli cells through the use of a BODIPY-labeled septanoside. The modularity of the indolyl septanoside synthesis should allow the screening of a variety of substrates that mimic natural structures via this general approach.

Original languageEnglish
Article number4497
JournalInternational Journal of Molecular Sciences
Volume22
Issue number9
DOIs
Publication statusPublished - 1 May 2021

Keywords

  • Glycosidase
  • Indolyl glycoside
  • Septanoside
  • Septanoside hydrolase

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