Plastics are essential to modern life, yet poor disposal practices contribute to low recycling rates and environmental accumulation-biological degradation and by-product reuse offer a path to mitigate...

Newer trials are starting to track Lyme patients and investigate potential treatments

Long cast as villains, some protists, such as Blastocystis, are potentially beneficial to human health.

Another reason why RFK Jrs. MAHA plan is misguided

Compositionality, the capacity to combine meaningful elements into larger meaningful structures, is a hallmark of human language. Compositionality can be trivial (the combination’s meaning is the sum ...

A team from the Institut de Ciències del Mar (ICM-CSIC), in collaboration with the Bellvitge Biomedical Research Institute (IDIBELL), has applied for the patent of two new “gene editing scissors” with...

ALT: a greeting card for eid-eh shoma mobarak wishing you a healthy and prosperous novruz

Enzymes are the quintessential green catalysts, but realizing their full potential for biotechnology typically requires improvement of their biomolecular properties. Catalysis enhancement, however, is often accompanied by impaired stability. Here, we show how the interplay between activity and stability in enzyme optimization can be efficiently addressed by coupling two recently proposed methodologies for guiding directed evolution. We first identify catalytic hotspots from chemical shift perturbations induced by transition-state-analogue binding and then use computational/phylogenetic design (FuncLib) to predict stabilizing combinations of mutations at sets of such hotspots. We test this approach on a previously designed de novo Kemp eliminase, which is already highly optimized in terms of both activity and stability. Most tested variants displayed substantially increased denaturation temperatures and purification yields. Notably, our most efficient engineered variant shows a ∼3-fold enhancement in activity (kcat ∼ 1700 s–1, kcat/KM ∼ 4.3 × 105 M–1 s–1) from an already heavily optimized starting variant, resulting in the most proficient proton-abstraction Kemp eliminase designed to date, with a catalytic efficiency on a par with naturally occurring enzymes. Molecular simulations pinpoint the origin of this catalytic enhancement as being due to the progressive elimination of a catalytically inefficient substrate conformation that is present in the original design. Remarkably, interaction network analysis identifies a significant fraction of catalytic hotspots, thus providing a computational tool which we show to be useful even for natural-enzyme engineering. Overall, our work showcases the power of dynamically guided enzyme engineering as a design principle for obtaining novel biocatalysts with tailored physicochemical properties, toward even anthropogenic reactions.

Countries are meeting to agree the first ever global treaty on curbing plastic pollution. Research suggests where bans and incentives can make a difference.