Engineering of Therapeutic and Detoxifying Enzymes

Michailidou, Freideriki

doi:10.1002/anie.202308814

Cited by 3 publications

(1 citation statement)

References 102 publications

(83 reference statements)

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“…They display great advantages in increasing reaction rates and have huge application potential in various industries, including biochemistry, pharmaceuticals, agriculture, and food. [ 1–5 ] However, the complex technical requirements in extraction, high costs in storage, poor structural and catalytic stability, and recycling difficulties largely limit their widespread applications. [ 6,7 ] Developing feasible methods to substitute natural enzymes is essential to spur the development of related industries.…”

Section: Introductionmentioning

confidence: 99%

Chiral Cu_xCo_yS‐Cu_zS Nanoflowers with Bioinspired Enantioselective Catalytic Performances

Si,

Wang,

Ding

et al. 2024

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Nanomaterials with biomimetic catalytic abilities have attracted significant attention. However, the stereoselectivity of natural enzymes determined by their unique configurations is difficult to imitate. In this work, a kind of chiral CuxCoyS‐CuzS nanoflowers (L/D‐Pen‐NFs) is developed, using porous CuxCoyS nanoparticles (NPs) as stamens, CuzS sheets as petals, and chiral penicillamine as surface stabilizers. Compared to the natural laccase enzyme, L/D‐Pen‐NFs exhibit significant advantages in catalytic efficiency, stability against harsh environments, recyclability, and convenience in construction. Most importantly, they display high enantioselectivity toward chiral neurotransmitters, which is proved by L‐ and D‐Pen‐NFs’ different catalytic efficiencies toward chiral enantiomers. L‐Pen‐NFs are more efficient in catalyzing the oxidation of L‐epinephrine and L‐dopamine compared with D‐Pen‐NFs. However, their catalytic efficiency in oxidizing L‐norepinephrine and L‐DOPA is lower than that of D‐Pen‐NFs. The reason for the difference in catalytic efficiency is the distinct binding affinities between CuxCoyS‐CuzS nano‐enantiomers and chiral molecules. This work can spur the development of chiral nanostructures with biomimetic functions.

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Section: Introductionmentioning

confidence: 99%

Chiral Cu_xCo_yS‐Cu_zS Nanoflowers with Bioinspired Enantioselective Catalytic Performances

Si,

Wang,

Ding

et al. 2024

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Genetically Engineered Liposwitch-Based Nanomaterials

Hossain,

Wang,

Anika

et al. 2024

Biomacromolecules

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Fusion of intrinsically disordered and globular proteins is a powerful strategy to create functional nanomaterials. However, the immutable nature of genetic encoding restricts the dynamic adaptability of nanostructures postexpression. To address this, we envisioned using a myristoyl switch, a protein that combines allostery and post-translational modifications�two strategies that modify protein properties without altering their sequence�to regulate intrinsically disordered protein (IDP)-driven nanoassembly. A typical myristoyl switch, allosterically activated by a stimulus, reveals a sequestered lipid for membrane association. We hypothesize that this conditional exposure of lipids can regulate the assembly of fusion proteins, a concept we term "liposwitching". We tested this by fusing recoverin, a calcium-dependent myristoyl switch, with elastin-like polypeptide, a thermoresponsive model IDP. Biophysical analyses confirmed recoverin's myristoyl-switch functionality, while dynamic light scattering and cryo-transmission electron microscopy showed distinct calcium-and lipidation-dependent phase separation and assembly. This study highlights liposwitching as a viable strategy for controlling DP-driven nanoassembly, enabling applications in synthetic biology and cellular engineering.

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Integrating Computational Design and Experimental Approaches for Next-Generation Biologics

Son,

Park,

Kim

et al. 2024

Biomolecules

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Therapeutic protein engineering has revolutionized medicine by enabling the development of highly specific and potent treatments for a wide range of diseases. This review examines recent advances in computational and experimental approaches for engineering improved protein therapeutics. Key areas of focus include antibody engineering, enzyme replacement therapies, and cytokine-based drugs. Computational methods like structure-based design, machine learning integration, and protein language models have dramatically enhanced our ability to predict protein properties and guide engineering efforts. Experimental techniques such as directed evolution and rational design approaches continue to evolve, with high-throughput methods accelerating the discovery process. Applications of these methods have led to breakthroughs in affinity maturation, bispecific antibodies, enzyme stability enhancement, and the development of conditionally active cytokines. Emerging approaches like intracellular protein delivery, stimulus-responsive proteins, and de novo designed therapeutic proteins offer exciting new possibilities. However, challenges remain in predicting in vivo behavior, scalable manufacturing, immunogenicity mitigation, and targeted delivery. Addressing these challenges will require continued integration of computational and experimental methods, as well as a deeper understanding of protein behavior in complex physiological environments. As the field advances, we can anticipate increasingly sophisticated and effective protein therapeutics for treating human diseases.

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Engineering of Therapeutic and Detoxifying Enzymes

Cited by 3 publications

References 102 publications

Chiral Cu_xCo_yS‐Cu_zS Nanoflowers with Bioinspired Enantioselective Catalytic Performances

Chiral Cu_xCo_yS‐Cu_zS Nanoflowers with Bioinspired Enantioselective Catalytic Performances

Genetically Engineered Liposwitch-Based Nanomaterials

Integrating Computational Design and Experimental Approaches for Next-Generation Biologics

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Engineering of Therapeutic and Detoxifying Enzymes

Cited by 3 publications

References 102 publications

Chiral CuxCoyS‐CuzS Nanoflowers with Bioinspired Enantioselective Catalytic Performances

Chiral CuxCoyS‐CuzS Nanoflowers with Bioinspired Enantioselective Catalytic Performances

Genetically Engineered Liposwitch-Based Nanomaterials

Integrating Computational Design and Experimental Approaches for Next-Generation Biologics

Contact Info

Product

Resources

About

Chiral Cu_xCo_yS‐Cu_zS Nanoflowers with Bioinspired Enantioselective Catalytic Performances

Chiral Cu_xCo_yS‐Cu_zS Nanoflowers with Bioinspired Enantioselective Catalytic Performances