# Nitrogenase assembly mechanism

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $384,696

## Abstract

PROJECT SUMMARY
Nitrogenase reaction represents a major source of the usable form of nitrogen that supports the
existence of human population. As such, understanding how small building blocks are
assembled into a functional nitrogenase entity is of significant relevance to human health. Using
combined genetic, biochemical, spectroscopic and structural approaches, we propose to
investigate how M-cluster, the unique metallocofactor of molybdenum nitrogenase, is
assembled into a functional unit. Specifically, we will investigate how an interstitial carbide is
inserted via a radical SAM-dependent mechanism concomitant with fusion of two 4Fe modules
into an 8Fe core of the M-cluster, what is the in vivo donor/carrier of the “9th sulfur” and how this
sulfur is inserted into the catalytically important belt region of the 8Fe core, and how Mo is
mobilized and inserted into the 8Fe core to form a mature M-cluster. Through our proposed
studies, we expect to further refine the biosynthetic pathway of the unique metallocofactor of
nitrogenase, which will provide crucial insights into the structural-functional relationship of this
important enzyme and reveal some general principles of the assembly mechanisms of complex
metalloclusters in biological systems.

## Key facts

- **NIH application ID:** 10141750
- **Project number:** 2R01GM067626-18
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Markus W Ribbe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,696
- **Award type:** 2
- **Project period:** 2003-05-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141750

## Citation

> US National Institutes of Health, RePORTER application 10141750, Nitrogenase assembly mechanism (2R01GM067626-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141750. Licensed CC0.

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