Abstract. The integration of artificial intelligence with protein engineering has created unprecedented opportunities for enzyme discovery and the enhancem

Abstract. N-Acetylglucosamine exists in various glycoforms and linkage patterns within organisms, playing a crucial role in numerous vital biological proce

AbstractPredicting the long-term stability of immobilized enzymes remains challenging due to the complex physicochemical interactions within immobilization

Transition state (TS) generation is typically evaluated by geometric similarity, yet low root-mean-square deviation (RMSD) does not establish first-order saddle-point character or reaction-path connec...

AbstractAntibody-directed enzyme prodrug therapy (ADEPT) utilizes a cancer-targeting antibody–enzyme conjugate to selectively activate a prodrug at the sit

Increasingly diverse sequence repositories can be accessed through advanced bioinformatics tools. Complementary screening assays accelerate the identification and engineering of improved amidases and urethanases that act on highly stable bonds in plastics such as polyamides and polyurethanes.

When reduced flavin is activated by molecular oxygen it forms a spin-correlated radical pair—a flavin semiquinone and superoxide (O₂•⁻)—born in the triplet manifold, because ground-state O₂ is a tripl...

Enzyme-based biomaterials are sustainable catalytic platforms with applications in biosensing, pharmaceutical synthesis, and environmental remediation. A key challenge is developing universal immobilisation strategies that preserve activity without ...

Natural enzyme families achieve functional breadth by diversifying a common scaffold into specialized enzymes. Engineering comparable family-like diversity for synthetic chemistry is challenging because directed evolution workflows frequently optimize one ...

Directed evolution is a powerful approach for enzyme engineering, but conventional workflows use only a fraction of the information generated during experimental screening. Typically, only top-performing variants are sequenced and propagated, while ...

Enzymatic synthesis of modified nucleic acids is gaining a lot of traction. Most approaches involve the combination of modified nucleoside triphosphates and engineered polymerases capable of accepting...

We introduce QMzyme, a Python package to automate the generation of Quantum mechanics (QM)-based enzyme models. QM calculations on enzymes are computationally challenging because full enzyme systems t...

Direct addition of free alcohols across alkenes would provide a concise route to chiral ethers, but controlling alkene activation, nucleophile capture, and stereochemistry remains difficult. We evolve...

In this work, two ketone-containing pre-polyesters based on dimethyl 2-oxoglutarate (pDMOG) and dimethyl 1,3-acetonedicarboxylate (pDADC), were obtained via a solventless polymerization reaction in presence of Lipase B from Candida antarctica as the ...

A standardized gas chromatography–based workflow enables direct functional screening of hydrogenase activity in crude membrane and lysate fractions from native bacteria. Without purification or heterologous expression, hydrogen oxidation is detected across phylogenetically diverse organisms, highlighting the value of activity-based screening for functional enzyme discovery. Functional assessment of hydrogenase activity in native bacterial systems is often complicated by the requirements associa…

Continuous-flow biocatalysis can decouple enzymatic productivity from the cellular growth constraints inherent to fermentation, but exploiting this advantage requires a reactor design framework that l...

Azo dyes are widespread in the environment, and humans ingest a range of these dyes present in food and drugs. The human gut microbiome significantly impacts the fate of ingested azo dyes primarily th...

AbstractTo address the inherent inertness of polylactic acid (PLA) nonwoven fabrics and the challenge of balancing grafting efficiency with biodegradabilit

Microbial transglutaminase (mTGase) readily forms intermolecular isopeptide bonds, but this native bias promotes peptide oligomerization at synthetically useful concentrations. Here we encode reaction...

A nontoxic proximity labeling approach is developed using an engineered D-amino acid oxidase and APEX2 fusion to generate H2O2 in situ from D-amino acids. It is applied in vivo in Caenorhabditis elegans, Drosophila, zebrafish and mice and has unique RNA labeling activity to probe RNA structures in vitro and in vivo.

A strategy is reported to prescreen and prioritize noncanonical amino acids as fragments prior to their use in mRNA display peptide libraries. Using MDM2 as a target, two ncAAs that bind to the Trp b...

Genetically encoded cyclic peptide libraries can be employed in cellular selection platforms to identify cyclic peptide inhibitors for therapeutic targets by directly selecting for desired biological...

The amino acid 4-difluoromethyl-L-phenylalanine was synthesized and incorporated into full-length proteins using an orthogonal aminoacyl-tRNA synthetase (aaRS) with standard genetic code expansion te...

Probes were rationally designed to capture key intramolecular interactions thorugh photocrosslinking in thiotemplated assembly lines: polyketide synthases (PKS), fatty acid synthases (FAS), and non-r...

Reversible photocontrol of enzymes can be achieved with the azobenzene-based photoswitchable unnatural amino acid AzoF. Screening of 85 AzoF incorporation positions in tryptophan synthase identified ...

A combination of directed evolution and process development is described in finding a transaminase suitable for manufacturing-scale synthesis of a chiral intermediate in the synthesis of niraparib.

Rubredoxin is a thermally stable thiolate iron-bound protein that can be prepared as a nickel-substituted one. This nickel protein showed sensitivity to reaction with NO and HNO donors, causing its d...

We developed a broad-host-range dual base editor that transiently induces genome-wide hypermutation, accelerating adaptive laboratory evolution by up to four orders of magnitude. The platform rapidly...

The valorisation of biological polymers requires microbial systems that can both access recalcitrant substrates and convert the resulting carbon into useful products. Although microbial genome and metagenome resources provide an expanding reservoir of candidate depolymerizing and modifying enzymes, most discovery workflows remain disconnected from enzyme optimisation and host adaptation. Here we present a coupled sequence-based enzyme discovery, enzyme evolution and synthetic yeast chassis adap…

Abstract. The increasing demands of synthetic biology have shifted the central bottleneck from DNA assembly to DNA writing. As engineered systems grow in c

Cytochrome P450 (CYP) enzymes with peroxygenase activity can use H2O2 as the sole oxidant which is beneficial for biocatalytic applications. We investigated the peroxygenase activity of CYP105D18 from Streptomyces laurentii. The modification of the acid-...

RNA modifications play an important role in biological processes. Mapping the diversity of RNA chemistry and studying the biological function of in...

AbstractAmino aldehyde intermediates exhibit extreme chemical lability, undergoing nonproductive cyclization and polymerization in bulk solvent at rates or

First direct observation of a quasi-reversible superoxo (FeIII─O2˙ˉ)/peroxo (FeIII─O22ˉ) redox couple in a heme model complex, featuring a biologically relevant low-spin ferric end-on peroxo species ...

De novo-designed enzymes have recently achieved high catalytic activity and stereoselectivity while demonstrating exceptional thermostability in entirely novel protein scaffolds. Among these, α-helica...

How allenes and alkynes are constructed in nature is poorly understood. Now, two fungal cytochrome P450 enzymes are shown to convert a common five-carbon prenyl group into four-carbon allene or alkyne motifs through oxidative C(sp2)-demethylation, establishing a biosynthetic carbon-editing strategy for generating these synthetically valuable functional groups.

Engineering redox enzymes to utilize noncanonical coenzymes is critical for advancing in vitro enzymatic biocatalysis and in vivo bioorthogonal chemistry. However, engineered NAD(P)-dependent dehydrog...

CoA transferases are crucial in fatty acid metabolism, yet their regulation by metabolic signals is not well understood. Here, the authors reveal a dual-layer regulatory mechanism in Thermus thermophilus, in which a pseudoenzyme mediates redox-dependent regulation of CoA transferase, while acetylation further modulates its activity.

Despite rapid advances in new-to-nature biocatalysis, trimolecular enzymatic reactions that generate previously inaccessible molecular entities, particularly those bearing well-defined, congested ster...

Biosynthesis and biocatalysis are increasingly integrated to reshape the landscape of sustainable chemistry. The translation of natural biosynthetic enzymes into viable practical biocatalysts remains ...

AbstractA ribozyme that can charge a tRNA with amino acids and discriminate between cognate and non-cognate tRNAs is of interest because an RNA with this a

Abstract. Accurate prediction of enzyme optimal pH (pHopt) is fundamental to biocatalyst engineering, pharmaceutical development, and process optimization,

Cytochrome P450 (CYP) monooxygenases are heme-thiolate enzymes that catalyze diverse oxidative transformations essential to metabolism, detoxification, and biosynthesis. While most CYPs rely on separa...

We report a single, fully genome-engineered Pseudomonas putida ETAB-HB V4 strain for valorizing complex plastic-derived feedstocks into (R)-3-hydroxybutyrate. The results support open-loop recycling s...

Abstract. Here we describe the construction of an artificial enzyme bearing a biomimetic PLP-like catalytic center within an apo-myoglobin scaffold through

Glucoamylase is essential for industrial starch saccharification, but the limited thermostability and near-neutral pH tolerance of fungal glucoamylases necessitate cooling and acidification of liquefi...

AbstractUnspecific peroxygenase (UPO) catalyzes selective oxyfunctionalization of C–H bonds using H2O2 but suffers from enzyme instability and substrate so

Abstract. AprD5 is a member of the NAD+-dependent short-chain dehydrogenase/reductase (SDR) superfamily. It participates in the apramycin biosynthetic path

Macaranga tanarius (Euphorbiaceae), a myrmecophilic plant grown in subtropical countries, was identified as a source of Okinawan propolis, a honeybee product, which is glandular trichomes developed on...

Abstract. Tyrosine-selective peptide modification provides a valuable route to late-stage diversification, yet current methods remain largely limited to si