Selective Enzymatic Oxidation of Silanes to Silanols

• Published in: Angewandte Chemie International Edition Vol. 59; no. 36; pp. 15507 - 15511
• Main Authors: Bähr, Susanne, Brinkmann‐Chen, Sabine, Garcia‐Borràs, Marc, Roberts, John M., Katsoulis, Dimitris E., Houk, K. N., Arnold, Frances H.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.09.2020
• Edition: International ed. in English
• Subjects: Bacillus megaterium - enzymology; Biocatalysis; Biotransformation; Catalysis; Catalysts; Computer applications; Cytochrome; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Cytochrome P450 monooxygenase; Cytochromes P450; Directed evolution; Enzymes; Evolution; Homology; Hydroxylation; Models, Molecular; monooxygenation; Oxidants; Oxidation; Oxidation-Reduction; Oxidizing agents; P450 enzymes; Silanes; Silanes - chemistry; Silanes - metabolism; silanols; Substrates; silanols; P450 enzymes; monooxygenation; biocatalysis; directed evolution
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202002861

Compared to the biological world's rich chemistry for functionalizing carbon, enzymatic transformations of the heavier homologue silicon are rare. We report that a wild‐type cytochrome P450 monooxygenase (P450BM3 from Bacillus megaterium, CYP102A1) has promiscuous activity for oxidation of hydrosilanes to give silanols. Directed evolution was applied to enhance this non‐native activity and create a highly efficient catalyst for selective silane oxidation under mild conditions with oxygen as the terminal oxidant. The evolved enzyme leaves C−H bonds present in the silane substrates untouched, and this biotransformation does not lead to disiloxane formation, a common problem in silanol syntheses. Computational studies reveal that catalysis proceeds through hydrogen atom ion followed by radical rebound, as observed in the native C−H hydroxylation mechanism of the P450 enzyme. This enzymatic silane oxidation extends nature's impressive catalytic repertoire. In rerum natura: Wild‐type cytochrome P450BM3 catalyzes the oxidation of hydrosilanes to silanols both in vivo and in vitro. Directed evolution was used to generate an efficient and selective biocatalyst that delivers a broad range of aryl‐ and alkyl‐substituted silanols. Computational studies revealed a sequence of H atom ion and OH rebound as the mechanism, in analogy to the native C−H hydroxylation activity.