Iron-sulfur protein catalyzed [4+2] cycloadditions

July 30, 2024

A prospective starting point for designing various Lewis acid catalysts

A joint research group of researchers from the RIKEN CSRS, the University of Shizuoka, and Osaka University demonstrated that iron-sulfur (Fe-S) protein works as a Lewis acid catalyst in natural product biosynthesis, accelerating [4+2] (Diels-Alder) cycloadditions.

The joint research group identified cytochrome P450 (VtlG), which catalyzes hydroxylation reaction, and an enzyme that catalyzes [4+2] cycloadditions (VtlF) in the biosynthesis of verticilactam (VTL), a secondary metabolite from Actinomyces. By effectively combining biochemical experiments and theoretical calculations, the group demonstrated that the Fe-S cluster in the enzyme molecule efficiently accelerates [4+2] cycloadditions.

This study is the first to demonstrate that natural enzymes working as Lewis acid catalysts accelerate [4+2] cycloadditions in natural product biosynthesis. This Fe-S protein well-known as electron carrier is now expected to be a prospective starting point for designing various Lewis acid catalysts for [4+2] cycloadditions.

Original article

Nature Communications doi: 10.1038/s41467-024-50142-1

Y. Zheng, K. Sakai, K. Watanabe, H. Takagi, Y. Sato-Shiozaki, Y. Misumi, Y. Miyanoiri, G. Kurisu, T. Nogawa, R. Takita, S. Takahashi,

"Iron-sulphur protein catalysed [4+2] cycloadditions in natural product biosynthesis".

Contact

Shunji Takahashi; Unit Leader
Yu Zheng; Special Postdoctoral Researcher
Katsuyuki Sakai; Postdoctoral Researcher
Natural Product Biosynthesis Research Unit