# Mechanisms of Arsenic Transport and Biotransformations

> **NIH NIH R35** · FLORIDA INTERNATIONAL UNIVERSITY · 2020 · $111,000

## Abstract

Project Summary/Abstract: Arsenic is the most pervasive toxin, considered by the EPA to be
one the most significant potential environmental threats to human health. Arsenic exposure is a
cause of cancer, heart disease and childhood developmental delay. Our research program
focuses on arsenic transporters and biotransformations, which modify its availability, speciation,
mobility and toxicity. We are uniquely qualified for this project: over the lifetime of this grant, my
group identified and characterized the majority of ars genes/proteins involved in arsenic transport,
biotransformations and resistance and their impact on the global arsenic biogeocycle. We
discovered enzymes of the arsenic methylation cycle and elucidated mechanisms and structures
of the enzymes of biotransformation, developed biosensors for organoarsenicals herbicides and
discovered organoarsenicals that are novel antimicrobial agents. My goals for the next five years
fall into four categories. 1) Structure/function analysis of enzymes of arsenic biotransformations.
We will elucidate the catalytic cycle of the ArsM arsenite S-adenosylmethione (SAM)
methyltransferase, the ArsH methylarsenite oxidases, the ArsI C-As bond lyases and the ArsN
N-acetyltransferase through biochemical and structural analysis. 2) Regulation and biosensing.
We will determine the structural details of metalloregulation. We will devise new applications for
sensing environmental organoarsenical pollutants. 3) Arsenic transporters; we identified a
number of new permeases for organoarsenicals and will determine the mechanism of transport
by a combination of molecular genetics, biochemistry and crystallography. 4) Arsenical antibiotics;
we recently identified two organoarsenical natural products with antibiotic activity. We will
determine the pathways of synthesis and mode of action of these novel compounds and discover
new natural products with potential health applications. My overall vision is a research program
of sufficient breadth to encompass identification of the physiological roles of known arsenic
resistance genes and sufficient depth to elucidate their molecular mechanisms. Microbial
genomes have many uncharacterized arsenic-related genes. There are predicted permeases
and enzymes with no known substrate or function. We predict these are involved in arsenical
transport or biotransformations. We will mine microbial genomes for new ars genes, deduce their
evolutionary histories and determine how they effect cycling of environmental arsenicals. We will
discover their physiological functions. Their protein products will be purified and characterized by
biochemical and structural analyses. My overarching theme is to make substantial contributions
to understanding of the global arsenic biogeocycle and its impact on human health.

## Key facts

- **NIH application ID:** 10134719
- **Project number:** 3R35GM136211-01S1
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** BARRY P. ROSEN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $111,000
- **Award type:** 3
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134719

## Citation

> US National Institutes of Health, RePORTER application 10134719, Mechanisms of Arsenic Transport and Biotransformations (3R35GM136211-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134719. Licensed CC0.

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