Loop dynamics and the evolution of enzyme activity

M Corbella, GP Pinto, SCL Kamerlin - Nature Reviews Chemistry, 2023 - nature.com
In the early 2000s, Tawfik presented his 'New View'on enzyme evolution, highlighting the
role of conformational plasticity in expanding the functional diversity of limited repertoires of …

β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates

M Mora-Ochomogo, CT Lohans - RSC Medicinal Chemistry, 2021 - pubs.rsc.org
The β-lactams are the most widely used antibacterial agents worldwide. These antibiotics, a
group that includes the penicillins and cephalosporins, are covalent inhibitors that target …

Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase

C Fröhlich, HA Bunzel, K Buda, AJ Mulholland… - Nature Catalysis, 2024 - nature.com
Epistasis, the non-additive effect of mutations, can provide combinatorial improvements to
enzyme activity that substantially exceed the gains from individual mutations. Yet the …

Within-patient evolution of plasmid-mediated antimicrobial resistance

J DelaFuente, L Toribio-Celestino… - Nature ecology & …, 2022 - nature.com
Antimicrobial resistance (AMR) in bacteria is a major threat to public health; one of the key
elements in the spread and evolution of AMR in clinical pathogens is the transfer of …

Evolution of β-lactamase-mediated cefiderocol resistance

C Fröhlich, V Sørum, N Tokuriki… - Journal of …, 2022 - academic.oup.com
Background Cefiderocol is a novel siderophore β-lactam with improved hydrolytic stability
toward β-lactamases, including carbapenemases, achieved by combining structural …

Rational enzyme design by reducing the number of hotspots and library size

Z Qin, B Yuan, G Qu, Z Sun - Chemical Communications, 2024 - pubs.rsc.org
Biocatalysts that are eco-friendly, sustainable, and highly specific have great potential for
applications in the production of fine chemicals, food, detergents, biofuels, pharmaceuticals …

Recent developments to cope the antibacterial resistance via β-lactamase inhibition

Z Iqbal, J Sun, H Yang, J Ji, L He, L Zhai, J Ji, P Zhou… - Molecules, 2022 - mdpi.com
Antibacterial resistance towards the β-lactam (BL) drugs is now ubiquitous, and there is a
major global health concern associated with the emergence of new β-lactamases (BLAs) as …

The role of antibiotic resistance genes in the fitness cost of multiresistance plasmids

F Rajer, L Sandegren - MBio, 2022 - Am Soc Microbiol
By providing the bacterial cell with protection against several antibiotics at once,
multiresistance plasmids have an evolutionary advantage in situations where antibiotic …

β-lactamase expression induces collateral sensitivity in Escherichia coli

C Herencias, L Álvaro-Llorente… - Nature …, 2024 - nature.com
Major antibiotic groups are losing effectiveness due to the uncontrollable spread of
antimicrobial resistance (AMR) genes. Among these, β-lactam resistance genes–encoding β …

Evolution of β-lactamases and enzyme promiscuity

C Fröhlich, JZ Chen, S Gholipour… - Protein Engineering …, 2021 - academic.oup.com
Abstract β-Lactamases represent one of the most prevalent resistance mechanisms against
β-lactam antibiotics. Beyond their clinical importance, they have also become key models in …