# Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions

> **NIH NIH R01** · PENNSYLVANIA STATE UNIVERSITY, THE · 2021 · $328,749

## Abstract

Project Summary/Abstract
Enzymes that use coupled di-iron clusters that are coordinated by carboxylate and
histidine residues to activate dioxygen for difficult oxidation reactions play crucial roles in
the global carbon cycle, in DNA biosynthesis, and in synthesis of clinically used natural-
product drugs. In this last year, a new structural family of diiron enzymes has come into
focus. Related in structure to heme-oxygenase (HO), these HO-like diiron oxidase and
oxygenases (HODOs) have already expanded the known catalytic repertoire of the diiron
unit, even with only four members of the new family having been assigned biochemical
functions. In their functions, these HO-like enzymes produce antibiotics (the
nitroimidazoles), cancer drugs (streptozotocin), and jet fuel. Moreover, they appear to
function in a manner that is distinct from the functional paradigm that was established by
earlier work on other systems. Rather than remaining as stable cofactors within the HO-
proteins scaffolds, they spontaneously degrade, at least in vitro, perhaps as part of a
novel modus operandi that eliminates the requirement for cooperating proteins in their
catalytic cycles. The goal of this project is to understand the structures and mechanisms
of the first four functionally assigned members of what appears, on the basis of
bioinformatic analysis, to be a large and versatile new enzyme family. The expectation is
that an understanding of its functional principles might enable the new family to become a
privileged scaffold for directed evolution of new synthetically useful enzyme activities.

## Key facts

- **NIH application ID:** 10208910
- **Project number:** 5R01GM138580-02
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** JOSEPH M BOLLINGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,749
- **Award type:** 5
- **Project period:** 2020-07-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208910

## Citation

> US National Institutes of Health, RePORTER application 10208910, Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions (5R01GM138580-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10208910. Licensed CC0.

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