Enzymatic Strategies for Nitrogen-Nitrogen Bond Formation in Natural Product Biosynthesis
Jingkun Shi1, Guiyun Zhao1, Yi-Ling Du1
1Institute of Pharmaceutical Biotechnology and Department of Microbiology, School of Medicine, Zhejiang University, 310058 Hangzhou, China.
Chemical Reviews
|April 22, 2026
Summary
Nature employs diverse enzymes to create challenging nitrogen-nitrogen (N-N) bonds found in pharmaceuticals. This review details key enzyme families and biosynthetic pathways for N-N bond formation, aiding biocatalyst development.
Area of Science:
- Biochemistry
- Enzymology
- Natural Product Synthesis
Background:
- Nitrogen-nitrogen (N-N) bonds are crucial structural elements in many pharmaceuticals and bioactive natural products.
- Forming N-N bonds enzymatically presents significant chemical challenges, yet nature has evolved diverse strategies.
Purpose of the Study:
- To review the discovery and mechanistic understanding of enzymes responsible for biological N-N bond formation.
- To summarize biosynthetic pathways of natural products containing N-N bonds.
- To provide a foundation for biocatalyst development and genome-driven discovery of novel bioactive compounds.
Main Methods:
- Literature review of recent advances in genomics and biochemistry related to N-N bond formation.
- Highlighting key enzyme families: heme-dependent hydrazine synthases, zinc-dependent hydrazine synthetases, ATP-dependent diazotases/N-nitrosylases, and membrane-bound enzymes.
- Summarizing biosynthetic pathways and emphasizing enzyme catalytic mechanisms.
Main Results:
- Identification and characterization of multiple enzyme families catalyzing N-N bond formation.
- Elucidation of enzymatic strategies for forging these challenging chemical linkages.
- Detailed review of N-N bond-containing natural product biosynthesis.
Conclusions:
- Understanding the enzymology of N-N bond formation is expanding through biological studies.
- Knowledge of these enzymes and pathways can drive the development of novel biocatalysts.
- This work facilitates the genome-driven discovery of new bioactive compounds featuring N-N bonds.
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