# MECHANISMS OF ARSENIC TRANSPORT AND BIOTRANSFORMATIONS

> **NIH NIH R35** · FLORIDA INTERNATIONAL UNIVERSITY · 2022 · $463,153

## 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, childhood developmental delay, and disrupts the human microbiome. Our research program
blossomed during the current funding period of our NIGMS grant, focusing 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 with the potential to be 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
affect 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:** 10374036
- **Project number:** 5R35GM136211-03
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** BARRY P. ROSEN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $463,153
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374036

## Citation

> US National Institutes of Health, RePORTER application 10374036, MECHANISMS OF ARSENIC TRANSPORT AND BIOTRANSFORMATIONS (5R35GM136211-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10374036. Licensed CC0.

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