Plug-and-Play Functionalization of Protein–Polymer Conjugates for Tunable Catalysis Enabled by Genetically Encoded “Click” Chemistry

Abstract

Protein−polymer conjugates have been widely fabricated and used in many areas across biotechnology and medicine. However, their functions and applications are often limited due to the selected and unchangeable proteins and polymers in the conjugates. To address this constraint, here, we design and fabricate protein−polymer conjugates as generic materials that can be postfunctionalized in a plug-and-play means for tunable catalysis. The key idea is to use genetically encoded "click" chemistry (i.e., SpyTag/SpyCatcher) to functionalize premade conjugates with versatile catalytic moieties. This process can protect the function/activity of ligated moieties from exposure to harsh chemical reactions. To enable easy recyclability, the conjugates are encapsulated in hydrogels before the "click" reaction. Using a biocatalyst and a nanocatalyst as models, we demonstrate the success of using two functionalized hydrogels for efficient catalytic reactions. In addition, the two catalysts can be coupled to perform a two-step artificial chemoenzymatic cascade reaction. Notably, the hydrogel-based catalytic materials allow for easy recovery and reuse for multiple cycles. We anticipate that our strategy will help create easy-to-use materials for catalysis and chemical (bio)transformations.

Efficient Enzyme‐Metal Hybrid Catalysts Constructed with Polymer

“…More recently, Li and co-workers co-immobilized β-galactosidase (LacZ) and AuNPs in a hydrogel constructed by using PNIPAAm as the building block. [21] In this process, a scaffold protein without biological activity is used to make the protein-PNIPAAm conjugate and the bioactive protein and metal nanoparticles were ligated to the scaffold protein via "click" chemistry of the SpyTag/SpyCatcher system (Figure 5). The LacZ-AuNPs-PNIPAAm hybrid catalyst was applied in a one-pot chemoenzymatic cascade reaction to convert o-nitrophenyl-β-Dgalactopyranoside (ONPG) to o-aminophenol (OAP) with onitrophenol (ONP) as the intermediate.…”

“…The CuS@G5-PEG/GOD hybrid catalyst has a better catalytic activity than the Fe3O4-GOD-base system in killing of reachable tumor tissue under NIR irradiation. [21] Copyright 2022, American Chemical Society.…”

“…More recently, Li and co‐workers co‐immobilized β‐galactosidase (LacZ) and AuNPs in a hydrogel constructed by using PNIPAAm as the building block [21] . In this process, a scaffold protein without biological activity is used to make the protein‐ PNIPAAm conjugate and the bioactive protein and metal nanoparticles were ligated to the scaffold protein via “click” chemistry of the SpyTag/SpyCatcher system (Figure 5).…”

“…b) Plug‐and‐play functionalization of protein–polymer conjugate‐based hydrogels enables tunable chemoenzymatic catalysis. Reproduced with permission [21] . Copyright 2022, American Chemical Society.…”

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

“…Polymers are holding breakthrough advantages for customizing protein catalysts. , Unlike time-consuming genetic evolution, , polymer catalysts can be modularly designed with a high degree of specificity and tunability in a short period of time. − The development of various polymerization methods allows for the fine-tuning of structures and density of catalytic species based on structure–property relations. − Combined with an in-depth understanding of catalytic reaction mechanisms, tailored catalysts can be easily developed to have improved catalytic reactivity and beneficial macromolecular effects. − Despite these merits, the application of polymer catalysts in modular design of artificial enzymes is still limited.…”