A combinatorially complete epistatic fitness landscape in an enzyme active site

KE Johnston, PJ Almhjell, EJ Watkins-Dulaney… - Proceedings of the …, 2024 - pnas.org
Protein engineering often targets binding pockets or active sites which are enriched in
epistasis—nonadditive interactions between amino acid substitutions—and where the …

Electric Fields Are a Key Determinant of Carbapenemase Activity in Class A β-Lactamases

H Jabeen, M Beer, J Spencer, MW Van der Kamp… - ACS …, 2024 - ACS Publications
Resistance to antibiotics is a public health crisis. Although carbapenems are less
susceptible to resistance than other β-lactam antibiotics, β-lactamases mediating resistance …

Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D

H Lee, H Park, K Kwak, C Lee, J Yun… - Journal of Enzyme …, 2025 - Taylor & Francis
Abstract β-lactams have been the most successful antibiotics, but the rise of multi-drug
resistant (MDR) bacteria threatens their effectiveness. Serine β-lactamases (SBLs), among …

Nature's Toolbox for the Hydrolysis of Lactams and Cyclic Imides

P Stockinger, R Buller - ACS Catalysis, 2024 - ACS Publications
Hydrolytic enzymes, such as lactamases or hydantoinases, can be valuably applied to
convert lactams (cyclic amides) and cyclic imides into optically pure compounds, for …

Active Learning-Assisted Directed Evolution

J Yang, RG Lal, JC Bowden, R Astudillo, MA Hameedi… - bioRxiv, 2024 - biorxiv.org
Directed evolution (DE) is a powerful tool to optimize protein fitness for a specific application.
However, DE can be inefficient when mutations exhibit non-additive, or epistatic, behavior …

Mechanism-Guided Computational Design Drives meso-Diaminopimelate Dehydrogenase to Efficient Synthesis of Aromatic d-amino Acids

T Wu, Y Chen, W Wei, W Song, J Wu, J Wen… - ACS Synthetic …, 2024 - ACS Publications
Aromatic d-amino acids (d-AAs) play a pivotal role as important chiral building blocks and
key intermediates in fine chemical and drug synthesis. Meso-diaminopimelate …

Concluding Remarks: Biocatalysis

UT Bornscheuer - Faraday Discussions, 2024 - pubs.rsc.org
Biocatalysis is a rapidly evolving field with increasing impact in organic synthesis, chemical
manufacturing and medicine. The Faraday Discussion reflected the current state of …

Variations and predictability of epistasis on an intragenic fitness landscape

S Baheti, N Raj, S Saini - bioRxiv, 2024 - biorxiv.org
How epistasis hinders or facilitates movement on fitness landscapes has been a
longstanding question of interest. Several high throughput experiments have demonstrated …

[PDF][PDF] Coiled double amyloid-like fibrils allosterically catalyze hydrolysis of β-lactam antibiotics

SM Kunnath, E Arad, R Zalk, I Kass, A Batushansky… - chemrxiv.org
The release of antibiotic compounds into wastewater constitutes a significant and growing
health and environmental hazard, particularly contributing to the spread of antibiotic …