# Characterization of new methanobactins and their biosynthetic enzymes

> **NIH NIH F32** · NORTHWESTERN UNIVERSITY · 2020 · $28,878

## Abstract

Project Summary/Abstract
 Methanobactins (Mbns) are ribosomally-synthesized and post-translationally modified
peptide natural products produced by methanotrophic (methane-oxidizing) bacteria to obtain
copper from the environment; copper is necessary for their primary metabolic enzyme, copper-
dependent particulate methane monooxygenase (pMMO). Previously characterized Mbns
contain a peptidic backbone with two heterocycle/thioamide pairs that provide two nitrogen and
two sulfur ligands for Cu(I). These Mbns bind copper with high affinity and specificity, and are
under investigation as drug candidates for human diseases of copper metabolism. Recent
bioinformatics studies have revealed that there are new types of Mbns that are predicted to
differ in structure and chemical properties from previously characterized Mbns. Moreover,
several uncharacterized enzymes that are expected to be involved in the biosynthesis of these
new Mbns are not well understood. In this project, uncharacterized Mbns with predicted novel
structures will be explored, and the enzymes responsible for their biosynthesis will be studied by
both in vivo and in vitro approaches. This research will provide significant insights into the
diversity of Mbn structures and functions, will elucidate new enzymatic chemistries, and will
impact development of Mbns and Mbn-like molecules as therapeutics.
 A multifaceted training program has been planned. Training in a variety of biochemical
and genetic as well as spectroscopic/spectrometric techniques needed to isolate and
characterize Mbns and their biosynthetic enzymes will be provided in the Rosenzweig laboratory.
In addition, formal training opportunities outside the laboratory, such as programs at the Life
Sciences Collaborative Access Team (LS-CAT) beamlines at the Advanced Photon Source
(APS) at Argonne National Laboratory and at the Penn State University Bioinorganic Training
Workshop, both of which are closely related to the proposed research, will be available. The
Department of Molecular Biosciences at Northwestern University is equipped with all the
equipment and resources necessary to conduct this research. In particular, collaborations with
the Hoffman laboratory for electron paramagnetic resonance (EPR) spectroscopy, Dr. Zhang at
the Integrated Molecular Structure Education and Research Center (IMSERC) for a suite of
NMR spectroscopic techniques, and Kelleher group for mass spectrometry will facilitate carrying
out this research. These training opportunities combined with the collaborative and scientific
environment at Northwestern University will ensure the success of the proposed research and
will provide excellent preparation for an independent, interdisciplinary research career.

## Key facts

- **NIH application ID:** 10228366
- **Project number:** 3F32GM131665-02S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Yun Ji Park
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,878
- **Award type:** 3
- **Project period:** 2019-02-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228366

## Citation

> US National Institutes of Health, RePORTER application 10228366, Characterization of new methanobactins and their biosynthetic enzymes (3F32GM131665-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10228366. Licensed CC0.

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