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Here, the authors show that cystatin C (CST3) regulates the activity of cathepsin B during pancreatitis in a pH dependent manner. Moreover, cathepsin B activity is inhibited by monomeric CST3 but activated by dimeric CST3.

β-Branched aromatic α-amino acids are valuable building blocks in natural products and pharmaceutically active compounds, but their synthesis is challenging due to the presence of two stereocenters. Here, the authors design phenylalanine ammonia lyases variants for the direct asymmetric synthesis of β-branched aromatic α-amino acids and reveal the reasons for enzyme’s inability to accept β-methyl cinnamic acid.

Carbohydrate esterases alter polysaccharides by removing ester groups. Here, the authors resolved crystal structures of two CE20 enzymes and discovered a novel, water-mediated catalytic triad essential for activity, offering insights into enzyme function and mechanism.

Phytoplankton blooms provoke bacterioplankton blooms, from which bacterial biomass (necromass) is released via zooplankton grazing and viral lysis. Here, Beidler et al. show that the bacterial biomass, including alpha-glucan polysaccharides generated from the consumption of algal organic matter, is reused by microbes in vitro and during a diatom-dominated bloom.

Over the past ten years, protein engineering has established biocatalysis as a practical and environmentally friendly alternative to traditional forms of catalysis both in the laboratory and in industry.

Fast screening of enzymes is key for directed evolution of industrial biocatalysts. Here, the authors report a simple, high-throughput, and low-equipment-dependent growth selection system for engineering three enzymes for synthesis of chiral amines.

A method has been devised that allows a ketoreductase enzyme to catalyse reactions other than its natural ones. The key is to excite the enzyme's cofactor using light – an approach that might work for other enzymes. See Letter p.414

Recently developed advanced microfluidics-based systems have outperformed known screening tools with respect to throughput, flexibility, sensitivity and tricks for hit recovery. This has enabled the discovery of novel and improved proteins from random mutagenesis libraries or metagenome-based sources.

Directed evolution commonly relies on point mutations but InDels frequently occur in evolution. Here the authors report a protein-engineering framework based on InDel mutagenesis and fragment transplantation resulting in greater catalysis and longer glow-type bioluminescence of the ancestral luciferase.

Elucidation of a multi-enzyme pathway for degradation of the polysaccharide ulvan by Formosa agariphila provides tools to use ulvan biomass from marine algal blooms as feedstock for renewable sources of carbohydrates.

Plastic polymer PET degrading enzymes are of great interest for achieving sustainable plastics recycling. Here, the authors present the crystal structures of the plastic degrading bacterial enzymes PETase, MHETase in its apo-form and MHETase bound to a non-hydrolyzable substrate analog.

The identification or development of enzymes with new functions remains a significant challenge. A new strategy uses rationally selected sequences anticipated to serve as functional motifs to search the wealth of available genomic data, successfully yielding 17 (R)-selective amine transaminases.

A motif was identified in the scaffold of an (S)-selective transaminase that enables the asymmetric synthesis of bulky chiral amines. This motif is transferable to other enzymes with as low as 70% sequence identity. The biocatalysts developed show high stereoselectivity and their synthetic potential was confirmed in preparative scale synthesis.

By enriching productive mutational paths, a Kemp eliminase that speeds up proton abstraction >10⁸-fold was developed in only five evolution rounds. Recombining it with a variant differing by 29 substitutions revealed the underlying fitness landscape.

AMP-forming acetyl-CoA synthetase (AcsA) is an essential enzyme in all domains of life. Here, the authors provide mechanistic insights into regulation of AcsA by lysine acetylation, uncovering a regulatory phosphotransacetylase activity.

Plastics play an essential role in modern life, but their uncontrolled disposal has led to severe environmental impacts. Sustainable strategies for reusing plastics waste are urgently needed. This Perspective examines biotechnological solutions for plastics recycling and upcycling, with an emphasis on the process-oriented challenges involved in achieving a circular plastics economy.

Protein improvement strategies today involve widely varying combinations of rational design with random mutagenesis and screening. To make further progress—defined as making subsequent protein engineering problems easier to solve—protein engineers must critically compare these strategies and eliminate less effective ones.

Surface-enhanced resonance Raman scattering enables rapid and sensitive identification of lipase activity and enantioselectivity on dispersed silver nanoparticles.

The late-stage functionalization of unactivated carbon–hydrogen bonds is a difficult but important task, which has been met with promising but limited success through synthetic organic chemistry. Here the authors use machine learning to engineer WelO5* halogenase variants, which led to regioselective chlorination of inert C–H bonds on a representative polyketide that is a non-natural substrate for the enzyme.

Considerable research achievements were made to address the plastic crisis using biotechnology, but this is still limited to polyesters. This Comment aims to clarify important aspects related to myths and realities about plastic biodegradation and suggests distinct strategies for a bio-based circular plastic economy in the future.

Significant process has been made in using one carbon sources toward biomanufacturing. Here, the authors explore how to strength its competitiveness, and highlight latest technologies and the released patents.

Enzymatic depolymerization of polyethylene terephthalate (PET) towards monomer recycling is a promising strategy for a bio-based circular plastic economy, but progress is limited by the lack of standard guidelines for assessing and comparing the depolymerization efficiency catalysed by various PET hydrolases. In this Perspective, the authors identify critical research gaps in sourcing novel PET hydrolases and specify crucial requirements for selecting and optimizing them for specific application scenarios.

The search for novel biocatalysts for plastic degradation has recently become a hot topic. Now, multiple catalytic triads of well-known serine esterases were introduced into non-catalytic protein nanopores to enable the hydrolysis of PET nanoparticles.

The discovery of cytochrome P450 monooxygenases that catalyze oxidative demethylation of 6-O-methyl-d-galactose reveals a new activity of cytochrome P450 enzymes and their role in polysaccharide biomass degradation in marine bacteria.

Chemical and biological catalysts provide distinct advantages and disadvantages to the synthetic chemist. This Review focuses on efforts to combine chemo- and biocatalysts, outlining the opportunities achievable by this approach and also efforts to overcome any incompatibilities between these different systems.