TY - JOUR

T1 - Tailoring Protein-Polymer Conjugates as Efficient Artificial Enzymes for Aqueous Asymmetric Aldol Reactions

AU - Zhang, Ningning

AU - Wu, Changzhu

N1 - Funding Information: We are thankful for the financial support from the Independent Research Fund Denmark (DFF) in the framework of the DFF starting grant. Novo Nordisk Foundation is acknowledged for its generous funding. We thank Prof. Marion B. Ansorge-Schumacher for fruitful discussions and generous support. N.Z. is thankfui for the financial support from China Scholarship Council (No. 201606210135). We thank Jian Ning (University of Southern Denmark) for the water contact angle measurement. Publisher Copyright: © 2022 American Chemical Society. All rights reserved.

PY - 2022/11/18

Y1 - 2022/11/18

N2 - Artificial enzymes are becoming a powerful toolbox for selective organic syntheses. Herein, we first propose an advanced artificial enzyme by polymeric modularity as an efficient aldolase mimic for aqueous asymmetric aldol reactions. Based on an in-depth understanding of the aldolase reaction mechanism and our previous work, we demonstrate the modular design of protein-polymer conjugates by co-incorporating l-proline and styrene onto a noncatalytic protein scaffold with a high degree of controllability. The tailored conjugates exhibited remarkable catalytic performance toward the aqueous asymmetric aldol reaction of p-nitrobenzaldehyde and cyclohexanone, achieving 94% conversion and excellent selectivity (95/5 diastereoselectivity, 98% enantiomeric excess). In addition, this artificial enzyme showed high tolerance against extreme conditions (e.g., wide pH range, high temperature) and could be reused for more than four times without significant loss of reactivity. Experiments have shown that the artificial enzyme displayed broad specificity for various aldehydes.

AB - Artificial enzymes are becoming a powerful toolbox for selective organic syntheses. Herein, we first propose an advanced artificial enzyme by polymeric modularity as an efficient aldolase mimic for aqueous asymmetric aldol reactions. Based on an in-depth understanding of the aldolase reaction mechanism and our previous work, we demonstrate the modular design of protein-polymer conjugates by co-incorporating l-proline and styrene onto a noncatalytic protein scaffold with a high degree of controllability. The tailored conjugates exhibited remarkable catalytic performance toward the aqueous asymmetric aldol reaction of p-nitrobenzaldehyde and cyclohexanone, achieving 94% conversion and excellent selectivity (95/5 diastereoselectivity, 98% enantiomeric excess). In addition, this artificial enzyme showed high tolerance against extreme conditions (e.g., wide pH range, high temperature) and could be reused for more than four times without significant loss of reactivity. Experiments have shown that the artificial enzyme displayed broad specificity for various aldehydes.

KW - artificial enzymes

KW - asymmetric aldol catalysis

KW - l -proline catalysis

KW - polymer modularity

KW - protein-polymer conjugates

UR - http://www.scopus.com/inward/record.url?scp=85141678083&partnerID=8YFLogxK

U2 - 10.1021/acssynbio.2c00387

DO - 10.1021/acssynbio.2c00387

M3 - Article

C2 - 36343337

AN - SCOPUS:85141678083

VL - 11

SP - 3797

EP - 3804

JO - ACS synthetic biology

JF - ACS synthetic biology

SN - 2161-5063

IS - 11

ER -