July 5, 2018
Control of stereoselectivity in [4+2] cycloaddition
RIKEN CSRS researchers have discovered enzymes that play a role in selectively forming enantiomers in natural product biosynthetic pathways.
Ongoing discoveries in recent years of naturally occurring enzymes that catalyze the [4+2] cycloaddtion have been attracting attention. One of those enzymes is Fsa2, which is responsible for the stereospecific formation of trans-decalin (a bicyclic hydrocarbon) in the biosynthetic pathway of a fungal bioactive metabolite, equisetin. A RIKEN collaborative research group looked at phomasetin as an analogous compound to equisetin, identified its biosynthesis gene, and clarified that Phm7 is a homologue of Fsa2. They also succeeded in creating a phomasetin derivative with an unnatural configuration by modifying filamentous fungi to replace the phm7 gene with the fsa2 gene. These results represent the first successful example of production of a natural product derivative with an unnatural ring structure by altering the gene responsible for the [4+2] cycloaddition.
The results of this research show that by replacing enzymes responsible for the stereoselectivity of natural products, it is possible to create natural product derivatives with unnatural cyclic structures, and offers new guidelines for the rational design of natural products with complex skeletons.
Angewandte Chemie International Edition doi:10.1002/anie.201805050
N. Kato, T. Nogawa, R. Takita, K. Kinugasa, M.Kanai, M. Uchiyama, H. Osada, S. Takahashi,
"Control of the stereochemical course of [4+2] cycloaddition during trans-decalin formation by Fsa2-family enzymes".
Naoki Kato; Research Scientist
Shunji Takahashi; Unit Leader
Natural Product Biosynthesis Research Unit