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Prof. Lin Shuangjun’s Research Team Published Paper in ACS Catalysis

June 21, 2021      Author:

Recently,  Prof. Lin Shuangjun’s research team from the School of Life Sciences and Biotechnology, SJTU published a research paper titled “One-Pot Asymmetric Synthesis of an Aminodiol Intermediate of Florfenicol Using Engineered Transketolase and Transaminase” in ACS Catalysis, a top international journal. SJTU postgraduate student Liu Qi from the School of Life Sciences and Biotechnology is the first author; Prof. Lin Shuangjun is the corresponding author.

Based on the understanding of the catalytic mechanism and protein structure of transketolase (TK) and ω-transaminase (TA), an enzyme-substrate binding model was established by means of molecular docking. And a semi-rational mutagenesis strategy was designed to convert the stereoselectivity of TK, the enantioselectivity of TA and the selectivity of aldehyde and ketone. Using the engineered TK and TA, (1R,2R)-p-methylsulfonyl phenylserinol was biosynthesized with good yield (76%) and high stereoselectivity (96% de and >99% ee), which facilitated the development of a chemoenzymatic method for producing florfenicol.

This research was funded by the National Key R&D Program of China (2018YFA0901900) and the National Natural Science Foundation of China (21632007, 31425001).

 

Author: School of Life Sciences and Biotechnology, SJTU

Source: School of Life Sciences and Biotechnology, SJTU

Translated by Zhang Yue

Proofread by Xiao Yangning, Fu Yuhe

 

 

 

ABSTRACT:

Florfenicol is the 3′-fluoro derivative of thiamphenicol and has been widely used in veterinary medicine for its high antibacterial activity and safety. However, the development of simplified and environmentally friendly catalytic methods for the stereoselective production of florfenicol is a key challenge. Herein, we established a enzymatic one-pot reaction for the synthesis of an aminodiol intermediate of florfenicol bearing two stereocenters from industrial raw material 4-(methylsulfonyl) benzaldehyde by coupling transketolase (TK) and ω-transaminase (TA). The enantioselectivity of TK from E. coli was converted from (S) (93% ee) to (R) (95% ee), and we also inverted the enantiopreference (E(S) = 9 to E(R) = 12) and ketone/aldehyde substrate selectivity of TA ATA117 via structure-guided enzyme engineering. Docking calculations and molecular dynamics simulations of the wild-type and mutant enzymes unveiled the molecular basis for enzymatic stereocontrol. Using the engineered TK and TA, (1R,2R)-p-methylsulfonyl phenylserinol was biosynthesized with good yield (76%) and high stereoselectivity (96% de and >99% ee). Our work established an enzymatic synthetic route to (1R,2R)-p-methylsulfonyl phenylserinol, facilitating the development of a chemoenzymatic method for producing florfenicol.