Functional Characterization of Cross-Link Formation in Atropopeptide P450 Synthases
Abstract Biaryl cross-link-containing peptides make up an emerging class of ribosomally synthesized and post-translationally modified peptides (RiPPs). The C–C, C–N, and C–O cross-links in atropopeptides are installed by atropopeptide P450 synthases. In this work, we characterized three unknown atropopeptide P450 synthases (KutB, KutC, and NteB). Functional characterization of KutC and NteB provided the first in vitro analysis of atropopeptide P450 synthases and revealed that NteB generates both bridge-above and bridge-below atropisomers. Furthermore, docking models of KutB, KutC, and NteB, together with mutational analysis, suggested putative substrate recognition residues. This study provides important insights into the biosynthesis of atropopeptides.
Authors
- Takahiro Mori (ORCID: https://orcid.org/0000-0002-2754-5858)
- Huibin Wang (ORCID: https://orcid.org/0000-0002-0020-7197)
- Ikuro Abe (ORCID: https://orcid.org/0000-0002-3640-888X)
- Chin‐Soon Phan (ORCID: https://orcid.org/0000-0002-6500-696X)
- Jabal Rahmat Haedar (ORCID: https://orcid.org/0009-0003-3080-8430)
- Gints Šmits (ORCID: https://orcid.org/0000-0001-5044-4169)
- Stefano Donadio (ORCID: https://orcid.org/0000-0002-2121-8979)
- Abujunaid Habib Khan (ORCID: https://orcid.org/0009-0008-8086-5325)
- Viktors Romaņuks
- Vic Kiselov
Institutions
- Chang Gung University of Science and Technology (TW)
- National Sun Yat-sen University (TW)
- Riga Technical University (LV)
- University of Toyama (JP)
- National Institute of Research and Innovation (LV)
- The University of Tokyo (JP)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1021/acs.orglett.6c04211
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Sun Yat-sen University
- Ministry of Education, Culture, Sports, Science and Technology
- New Energy and Industrial Technology Development Organization
- Chang Gung University
- Institute of Natural Medicine, University of Toyama
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Fusion Oriented REsearch for disruptive Science and Technology
- HORIZON EUROPE Widening participation and spreading excellence