# Mechanisms of Biosynthetic Formation of Deoxy Sugars

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $443,011

## Abstract

ABSTRACT
The development of new pharmaceuticals and other agents of biomedical value has frequently relied on
discoveries made in the field of natural products research. Carbohydrates in particular often represent the key
components of these natural products and are critical to their biological activities. Many of these sugars are in
turn characterized by unique structural features, the introduction of which typically requires biosynthetic
transformations that have never been seen before. Those working in the field of drug discovery often hope to
harness these biosynthetic pathways and enzymes in their efforts to identify and engineer new medicines;
however, in order to fully realize the potential of synthetic biology, the unprecedented chemistry behind these
biological reactions must be understood at a fundamental level. Providing such a foundation is the ultimate goal
of our research efforts, and our aim has thus been to enrich the repertoire of tools available to natural product
chemists and synthetic biologists in their efforts to develop new pharmaceuticals for the benefit of human health.
In this spirit, we have identified several systems for further study in the next funding period. The first specific aim
focuses on the mechanism by which four-membered oxetane rings are created from five-membered furanose
rings during the biosynthesis of oxetanocin A and albucidin. This aim is a continuation of our previous studies
on B12-dependent radical SAM enzymes that catalyze ring contraction reactions. The two enzymes being studied
are unique in their class, because nearly all other examples characterized to date catalyze methylation reactions.
The second specific aim is a mechanistic investigation of the process by which the bridging oxygen in the
furanose ring of cytidine diphosphate is replaced with sulfur during biosynthesis of the Trojan horse antibiotic
albomycin δ2. This is a radical SAM enzyme catalyzed reaction reminiscent of radical-initiated sulfur insertion
reactions; however, it involves the unprecedented swapping of a ring-bridging oxygen for sulfur rather than the
insertion of sulfur into a carbon-hydrogen bond. The third specific aim is a biosynthetic analysis of the dioxane-
ring containing aminoglycoside spectinomycin as well as a mechanistic investigation of the dioxane-forming
reaction. Spectinomycin is an antibiotic with proven clinical value; however, the biosynthesis of its unusual
tricyclic structure, which involves radical-mediated chemistry, is still not understood. These research aims have
been carefully designed to include not only the study of new and interesting biochemical reactions but systems
that are already known to display properties of medicinal value and may thus be further capitalized on.
Consequently, the proposed research is intended to reveal new insights into the biosynthesis of atypical and
bioactive carbohydrates in order to strengthen the foundation for future biomedical and biotechnological research
at ...

## Key facts

- **NIH application ID:** 10209563
- **Project number:** 2R01GM035906-37
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** HUNG-WEN LIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $443,011
- **Award type:** 2
- **Project period:** 1986-01-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209563

## Citation

> US National Institutes of Health, RePORTER application 10209563, Mechanisms of Biosynthetic Formation of Deoxy Sugars (2R01GM035906-37). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10209563. Licensed CC0.

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