TY - JOUR
T1 - Switching the Stereopreference of TeSADH
T2 - Enabling Anti-Prelog Asymmetric Reduction of Aryl-Ring-Containing Ketones
AU - Sardauna, Auwal Eshi
AU - Abdulrasheed, Muhammad
AU - Takahashi, Masateru
AU - Takahashi, Etsuko
AU - Hamdan, Samir M.
AU - Musa, Musa M.
N1 - Publisher Copyright:
© 2024 Wiley-VCH GmbH.
PY - 2024/11/11
Y1 - 2024/11/11
N2 - The biocatalytic asymmetric reduction of prochiral ketones offers a promising approach for producing optically active secondary alcohols. Alcohol dehydrogenases (ADHs) are enzymes that facilitate the reversible conversion of prochiral ketones into their corresponding optically active secondary alcohols, and thus are pivotal for this process. Most ADHs adhere to Prelog's rule in determining the stereopreference for the asymmetric reduction of prochiral ketones. This study focuses on the ΔP84/A85G mutation of TeSADH, demonstrating its capability to reduce aryl-ring-containing ketones to their corresponding alcohols in anti-Prelog mode with high stereoselectivities. The study also highlights the crucial role of P84 in switching the stereopreference of TeSADH in the asymmetric reduction of aryl-ring-containing ketones. Furthermore, this mutant exhibits a broad substrate scope, including substrates accepted by the previously reported W110 mutants of TeSADH with opposite stereopreference. The ability to create mutants of the same enzyme with opposite stereopreferences presents intriguing opportunities for fascinating transformations, such as bienzymatic racemization, which can be utilized in dynamic kinetic resolution, and stereoinversion using two enantiocomplementary mutants of the same enzyme.
AB - The biocatalytic asymmetric reduction of prochiral ketones offers a promising approach for producing optically active secondary alcohols. Alcohol dehydrogenases (ADHs) are enzymes that facilitate the reversible conversion of prochiral ketones into their corresponding optically active secondary alcohols, and thus are pivotal for this process. Most ADHs adhere to Prelog's rule in determining the stereopreference for the asymmetric reduction of prochiral ketones. This study focuses on the ΔP84/A85G mutation of TeSADH, demonstrating its capability to reduce aryl-ring-containing ketones to their corresponding alcohols in anti-Prelog mode with high stereoselectivities. The study also highlights the crucial role of P84 in switching the stereopreference of TeSADH in the asymmetric reduction of aryl-ring-containing ketones. Furthermore, this mutant exhibits a broad substrate scope, including substrates accepted by the previously reported W110 mutants of TeSADH with opposite stereopreference. The ability to create mutants of the same enzyme with opposite stereopreferences presents intriguing opportunities for fascinating transformations, such as bienzymatic racemization, which can be utilized in dynamic kinetic resolution, and stereoinversion using two enantiocomplementary mutants of the same enzyme.
KW - Alcohol dehydrogenases
KW - Anti-prelog reduction
KW - Biocatalysis
KW - Enantiopure alcohols
KW - Stereopreference
UR - http://www.scopus.com/inward/record.url?scp=85208176348&partnerID=8YFLogxK
U2 - 10.1002/ejoc.202400366
DO - 10.1002/ejoc.202400366
M3 - Article
AN - SCOPUS:85208176348
SN - 1434-193X
VL - 27
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
IS - 42
M1 - e202400366
ER -