The Final Steps in Pseudoiodinine Biosynthesis Feature Ring-Contractive N–N Bond Formation
Pseudoiodinine (PSD) is a N-N bond-containing natural product with profound antimicrobial and antifungal activities. In this work, we have completed the PSD biosynthetic pathway by explicating the final three steps, which involve an enigmatic N-N bond formation in a ring contraction process. As a starting material, 1,6-didesmethyltoxoflavin (1,6-DDMT) is sequentially methylated by PsdF and PsdA to give 5-methoxy-6-desmethyltoxoflavin (5-OCH<sub>3</sub>-6-DMT), which then undergoes oxidative decarboxylation for the ring-contractive N-N bond formation to generate the pyrazole ring catalyzed by PsdB, a novel vicinal oxygen chelate superfamily (VOC) protein. This is the first enzyme in the VOC family to catalyze such a reaction, providing new insight into N-N bond formation.
Authors
- Yu‐Cheng Gu (ORCID: https://orcid.org/0000-0002-6400-6167)
- Shuangjun Lin (ORCID: https://orcid.org/0000-0001-9406-9233)
- Gongyou Chen (ORCID: https://orcid.org/0000-0003-1979-2880)
- Qing Shi (ORCID: https://orcid.org/0000-0001-7477-7312)
- Tingting Huang (ORCID: https://orcid.org/0000-0002-9747-7969)
- Ikuro Abe (ORCID: https://orcid.org/0000-0002-3640-888X)
- Ruihuan Yang (ORCID: https://orcid.org/0000-0002-6932-5300)
- Lei Zhu (ORCID: https://orcid.org/0000-0002-1800-4769)
- Lifang Zou (ORCID: https://orcid.org/0000-0003-2903-0142)
- Xiaozheng Wang (ORCID: https://orcid.org/0000-0001-7841-3073)
- Zixin Deng (ORCID: https://orcid.org/0000-0003-0724-3390)
Institutions
- Shanghai Jiao Tong University (CN)
- Syngenta (United Kingdom) (GB)
- State Key Laboratory of Synthetic Chemistry (CN)
- Ecologie microbienne (FR)
- Syngenta (China) (CN)
- State Key Laboratory of Microbial Metabolism
- The University of Tokyo (JP)
Publication Details
- Journal
- JACS Au
- Published
- 2025-06-11
- DOI
- https://doi.org/10.1021/jacsau.5c00358
- Citations
- 3
- Primary Topic
- Metalloenzymes and iron-sulfur proteins
- Type
- article
- Field-Weighted Citation Impact
- 1.09
Funders
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- National Key Research and Development Program of China