TY - JOUR
T1 - SilE-R and SilE-S - DABB Proteins Catalyzing Enantiospecific Hydrolysis of Organosilyl Ethers
AU - Pick, Lisa
AU - Oehme, Vivien
AU - Hartmann, Julia
AU - Wenzlaff, Jessica
AU - Tang, Qingyun
AU - Grogan, Gideon James
AU - Ansorge-Schumacher, Marion
N1 - © 2024 The Authors.
PY - 2024/5/16
Y1 - 2024/5/16
N2 - Silyl ethers fulfil a fundamental role in synthetic organic chemistry as protecting groups and their selective cleavage is an important factor in their application. We present here for the first time two enzymes, SilE-R and SilE-S, which are able to hydrolyze silyl ethers. They belong to the stress-response A/B barrel domain (DABB) family and are able to cleave the Si-O bond with opposite enantiopreference. Silyl ethers containing aromatic, cyclic or aliphatic alcohols and, depending on the alcohol moiety, silyl functions as large as TBDMS are accepted. The X-ray crystal structure of SilE-R, determined to a resolution of 1.98 Ȧ, in combination with mutational studies, revealed an active site featuring two histidine residues, H8 and H79, which likely act synergistically as nucleophile and Brønsted base in the hydrolytic mechanism, which has not previously been described for enzymes. Although the natural function of SilE-R and SilE-S is unknown, we propose that these ‘silyl etherases’ may have significant potential for synthetic applications.
AB - Silyl ethers fulfil a fundamental role in synthetic organic chemistry as protecting groups and their selective cleavage is an important factor in their application. We present here for the first time two enzymes, SilE-R and SilE-S, which are able to hydrolyze silyl ethers. They belong to the stress-response A/B barrel domain (DABB) family and are able to cleave the Si-O bond with opposite enantiopreference. Silyl ethers containing aromatic, cyclic or aliphatic alcohols and, depending on the alcohol moiety, silyl functions as large as TBDMS are accepted. The X-ray crystal structure of SilE-R, determined to a resolution of 1.98 Ȧ, in combination with mutational studies, revealed an active site featuring two histidine residues, H8 and H79, which likely act synergistically as nucleophile and Brønsted base in the hydrolytic mechanism, which has not previously been described for enzymes. Although the natural function of SilE-R and SilE-S is unknown, we propose that these ‘silyl etherases’ may have significant potential for synthetic applications.
U2 - 10.1002/anie.202404105
DO - 10.1002/anie.202404105
M3 - Article
SN - 1433-7851
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
ER -