Aglycone sterics-selective enzymatic glycan remodeling

Anwen Mao; Yan Zhang; Guyu Wang; Tong Zhong; Xinyu Chen; Haiqi Wang; Ran Xie; Xiaojian Wang; Lin Ding; Huangxian Ju

doi:10.1016/j.isci.2022.104578

Aglycone sterics-selective enzymatic glycan remodeling

iScience. 2022 Jun 13;25(7):104578. doi: 10.1016/j.isci.2022.104578. eCollection 2022 Jul 15.

Authors

Anwen Mao¹, Yan Zhang¹, Guyu Wang¹, Tong Zhong¹, Xinyu Chen², Haiqi Wang¹, Ran Xie^{2

3}, Xiaojian Wang⁴, Lin Ding^{1

3}, Huangxian Ju¹

Affiliations

¹ State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
² State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
³ Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
⁴ Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.

Abstract

Precision remodeling of glycans in their native environments is pivotal for understanding glycan-mediated biological events and has important biotechnological implications in fields of clinical diagnosis, glyco-immune checkpoint therapy, and so forth. However, the influence of aglycone-steric diversity on the selectivity of glycan remodeling has been largely overlooked, limiting the application in complex biological scenarios. Here, we report the achievement of aglycone sterics-selective enzymatic glycan remodeling by controlled grafting of functional polymers from glycoenzyme. Through tuning polymer length, a series of enzyme-polymer composites with varying substrate permeability are prepared, which afford an activity pattern-based differentiation strategy for aglycone sterics. This leads to the implementation of glycolipid's partner screening, and aglycone sterics-selective glycan remodeling in a complex biological environment. We further orchestrate the polymer length adjustment with external cues to regulate aglycone-steric selectivity in a multi-faceted fashion, resulting in an unexpected enhancement of glycolipid remodeling, and temporal control of glycan remodeling on live cells.

Keywords: Biochemistry; Biological sciences; Enzyme engineering; Glycobiology.