Directed evolution of hemeproteins for selective cyclizations
Organic Molecular Chemistry - Synthesis and Characterisation
Final Report Abstract
The originally planned project did not yield any positive results within the first months, hence I focused on the catalytic anti-Markovnikov oxidation of alkenes. It is a long-standing challenge in chemistry that was just recently addressed employing transition metal catalysts and enzymes, respectively. Here I expand the substrate scope for enzymatic anti-Markovnikov oxidation by aliphatic olefins. From engineering of a cytochrome P450 enzyme by directed evolution an enzyme variant emerged that exhibits significant anti-Markovnikov-oxidation activity on very distinct aliphatic olefins including octene, already outcompeting epoxidation by up to twofold. After further evolution for user defined substrates the anti-Markovnikov oxygenase can be combined with other catalysts in synthetic metabolic pathways to access a variety of challenging anti-Markovnikov functionalization reactions. Furthermore, the intermediately formed carbocation could be trapped by nucleophiles, opening another possibility for enzymatic production of heterocyclic compounds.
Publications
- Science 2017, 358 (6360), S. 215–218
Hammer, Stephan C.; Kubik, Grzegorz; Watkins, Ella; Huang, Shan; Minges, Hannah; Arnold, Frances H.
(See online at https://doi.org/10.1126/science.aao1482)
