On the biocatalytic cleavage of silicon–oxygen bonds: A substrate structural approach to investigating the cleavage of protecting group silyl ethers by serine-triad hydrolases

• Published in: Journal of molecular catalysis. B, Enzymatic Vol. 56; no. 1; pp. 24 - 28
• Main Authors: Maraite, Andy, Ansorge-Schumacher, Marion B., Ganchegui, Benjamin, Leitner, Walter, Grogan, Gideon
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 2009; Elsevier
• Subjects: Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Enzymes; Fundamental and applied biological sciences. Psychology; Methods. Procedures. Technologies; Protecting groups; Serine hydrolases; Silylethers; Tertiary acids; Enzymes; Tertiary acids; Serine hydrolases; Protecting groups; Silylethers; Protecting group; Oxygen; Biocatalysis; Ether; Enzyme; Serine; Substrate; Cleavage; Hydrolases
• ISSN: 1381-1177; 1873-3158
• DOI: 10.1016/j.molcatb.2008.04.006

The biotransformation of compounds containing silicon has recently been a subject of much interest. In this study, a variety of commercially available serine hydrolases were tested for their ability to catalyse the hydrolysis of the silicon–ether bond in a variety of silyl ethers. The hydrolysis of trimethylethoxysilane in buffer was not found to be accelerated by the presence of trypsin, chymotrypsin, or a variety of other lipase and protease enzymes. Cleavage of a range of alternative silyl ether substrates, including a trimethylsilyl (TMS) ether, by these hydrolases was also not observed, but, interestingly, only two of the enzymes tested were able to cleave a t-butyl α,α,α-carboxylate that was approximately isosteric with the TMS-protected substrate. This suggests that the cleavage of Si–O bonds by serine hydrolases, such as the cathepsin homolog silicatein-α, may be in part limited by steric effects, as the reactive centre in the substrate is always, by analogy to C-centred substrates, tertiary, and thus inherently sterically demanding regardless of the putative catalytic competence of the enzymes.