# The Chemistry and Biology of Galactofuranose-Containing Glycans

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $460,884

## Abstract

Project Summary/Abstract Section
The Corynebacterineae suborder encompasses many infectious agents, including deadly human
pathogens, such as Mycobacterium tuberculosis (M. tb). Many antibiotics used to treat M. tb
block steps in cell envelope assembly, underscoring the key role of this protective barrier. The
Corynebacterineae cell envelope is unique in that it is constructed from saccharide and lipid
building blocks that differ dramatically even from those used by other bacteria. One of the
central features of the Corynebacterineae cell envelope is the mycolyl arabinogalactan (mAG),
which is a glycoconjugate assembled from galactofuranose (Galf), arabinofuranose (Araf), and
mycolic acids. Most enzymes involved in mAG biosynthesis have been identified but when,
where, and how they function in live cells to construct and remodel the cell envelope is not
known. To elucidate these changes and their functional roles, the proposed aims focus on
developing new tools to probe, perturb, and exploit changes in the Corynebacterineae cell
envelope. The focus of Aim 1 is on generating a small molecule probe of the galactan—the only
major cell wall constituent for which no effective probes exist. The target enzyme is UDP-
galactopyranose mutase (UGM), which catalyzes the formation of the key building block
required for biosynthesis of the essential galactan. The small molecule probe that results can be
used to evaluate the consequences of blocking galactan assembly to understand the role of
galactan in the stability and integrity of the cell envelope in Corynebacterineae and to probe the
role of UGM in other organisms. Aim 3 focuses on the mycolyltransferases, which construct the
critical mycolic acid components of the cell envelope. The localization of these enzymes and the
timing of their activity in cell division is not known. To visualize mycolyltransferase activity in
live cells, we propose to devise fluorogenic probes that can pinpoint the sites of Ag85 activity
and reveal the interplay between mycolyltransferase activity and cell envelope assembly. We
anticipate that the probes described in Aim 3 can be used to develop assays for finding inhibitors
of cell division and for monitoring and detecting mycobacteria in real time. We expect that our
pursuit of the three aims shall uncover vulnerabilities in the defenses of mycobacteria and
corynebacteria that will lead to new antibiotic strategies.
Significance:
The overall objective of this application is to develop new chemical probes to understand how
the Corynebacterineae build and maintain their cell wall to survive. We anticipate that this
knowledge will lead ultimately to the identification of new strategies to treat infectious disease.

## Key facts

- **NIH application ID:** 9851321
- **Project number:** 5R01AI126592-05
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Laura L Kiessling
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $460,884
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851321

## Citation

> US National Institutes of Health, RePORTER application 9851321, The Chemistry and Biology of Galactofuranose-Containing Glycans (5R01AI126592-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851321. Licensed CC0.

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