Themed collection Biocatalysis
![](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/Ajax-GA-Loader.gif)
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
On synergy between ultrahigh throughput screening and machine learning in biocatalyst engineering
We explore strategies for drawing-up ‘fitness landscapes’ in sequence space with ultrahigh throughput (uHT) droplet microfluidics, review the current state of AI/ML in enzyme engineering and discuss how uHT datasets may be combined with AI/ML.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00065J
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Spiers Memorial Lecture: Engineering biocatalysts
Enzymes are being engineered to catalyze chemical reactions for many practical applications in chemistry and biotechnology.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00139G
Indigo production identifies hotspots in cytochrome P450 BM3 for diversifying aromatic hydroxylation
Indigo (+) and indigo (−) single variants and a combinatorial library, with mutations that enable the blue phenotype, were screened for their ability to hydroxylate a panel of 12 aromatic compounds using the 4-aminoantipyrine colorimetric assay.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00017J
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Concluding remarks: biocatalysis
The classes of compounds accessible via biocatalysis are as diverse as the concepts to make them, as presented at the Faraday Discussion on biocatalysis.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00127C
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Harnessing conformational dynamics in enzyme catalysis to achieve nature-like catalytic efficiencies: the shortest path map tool for computational enzyme redesign
It is challenging to identify enzyme mutations that enhance specific conformational changes.We develop the shortest path map method to address this challenge.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D3FD00156C
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Degradation of PET microplastic particles to monomers in human serum by PETase
This study provides the first evidence of hydrolysis of PET microplastics in human serum by esterases, to combat the microplastic contamination in humans.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00014E
Application of rational enzyme engineering in a new route to etonogestrel and levonorgestrel: carbonyl reductase bioreduction of ethyl secodione
We combine the selection and engineering of a carbonyl reductase enzyme with process development, to enable efficient and economically viable bioreduction of ethyl secodione to (13R,17S)-secol, the key chirality introducing intermediate en route to contraceptives etonogestrel and levonorgestrel.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00011K
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Developing deprotectase biocatalysts for synthesis
A 1 pot, 2 step deprotection biocatalytic cascade.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00016A
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Exploring the selectivity of cytochrome P450 for enhanced novel anticancer agent synthesis
This work exemplifies the use of machine-learned 3D structure predictors combined with molecular docking to generate poses for atomistic study via molecular dynamics, ultimately enabling rapid insight into a novel biosynthetic cascade.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00004H
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Retuning the potential of the electrochemical leaf
By changing an active site tyrosine in FNR (the enzyme central to the e-Leaf) its exclusivity for NADP(H) swaps to NAD(H). Here, an electrochemical study of this variant reveals that the reduction potential of its active site flavin has been retuned.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00020J
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
An efficient pyrrolysyl-tRNA synthetase for economical production of MeHis-containing enzymes
A highly efficient aminoacyl tRNA synthetase (G1PylRSMIFAF) has been developed to produce MeHis-containing proteins. High protein titres can be achieved with low ncAA concentrations (0.1 mM) enabling more economical production of MeHis-containing enzymes.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00019F
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Designing Michaelases: exploration of novel protein scaffolds for iminium biocatalysis
The study identified promising protein scaffolds for artificial enzyme development in iminium-ion catalysis, demonstrating activity and enantioselectivity in abiological Michael addition reactions.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00057A
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN
We have developed novel tools to characterize evolutionarily conserved non-covalent interactions in proteins. We showcase their application to understanding substrate specificity in class A β-lactamases, with potential impact for protein engineering.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00018H
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Surveying the scope of aromatic decarboxylations catalyzed by prenylated-flavin dependent enzymes
H/D exchange between substrate and solvent D2O provides a sensitive test for substrate activation in prenylated-flavin dependent enzymes. We show that a remarkably diverse range of molecules can be activated by one enzyme, ferulic acid decarboxylase.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00006D
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Computation-guided engineering of distal mutations in an artificial enzyme
In silico prediction of distal hotspots was used to introduce distal mutations in an artificial enzyme that improved its reactivity and thermostability by shifting its conformational distribution.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00069B
Enhancement of essential cofactors for in vivo biocatalysis
Boosting the biosynthesis of essential cofactors by addition of xylose reductase and lactose to enhance product synthesis using synthetic biology.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00013G
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Computational study of the mechanism of a polyurethane esterase A (PueA) from Pseudomonas chlororaphis
We investigate the possible molecular mechanism of polyurethane esterase A, previously identified as responsible for degradation of a polyester polyurethane sample in Pseudomonas chlororaphis.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00022F
Tuning the peroxidase activity of artificial P450 peroxygenase by engineering redox-sensitive residues
Engineering redox-sensitive residues dramatically increases the peroxidase activity of P450BM3 monooxygenase, providing new insights and a strategy for regulating P450s' promiscuous functionality.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00008K
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Oxygen-resistant [FeFe]hydrogenases: new biocatalysis tools for clean energy and cascade reactions
A game-changer [FeFe]hydrogenase was studied to dissect the mechanism of oxygen resistance and learn how to protect biocatalysts for hydrogen-driven reactions.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00010B
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
An engineered T7 RNA polymerase for efficient co-transcriptional capping with reduced dsRNA byproducts in mRNA synthesis
We have engineered a novel RNA polymerase, T7-68, that improves co-transcriptional incorporation of selected cap analogs and reduces dsRNA content, addressing manufacturing challenges and facilitating large-scale mRNA production.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00023D
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Towards controlling activity of a peptide asparaginyl ligase (PAL) by lumazine synthetase compartmentalization
We aim to compartmentalize a representative peptide asparaginyl ligase, OaAEP1-C247A, within protein containers to create artificial organelles with substrate sorting capability.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00002A
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
On the biocatalytic synthesis of silicone polymers
A biocatalytic approach for polydimethylsiloxane synthesis is demonstrated using silicatein-α, an enzyme from marine sponges that catalyses the hydrolysis and condensation of Si–O bonds.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00003J
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
High-throughput selection of (new) enzymes: phage display-mediated isolation of alkyl halide hydrolases from a library of active-site mutated epoxide hydrolases
Epoxide hydrolase StEH1 was subjected to targeted randomized mutagenesis at five active-site amino acid residues and the resulting protein library was challenged for reactivity towards a bait chloride substrate.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00001C
![Open Access](https://www.rsc-cdn.org/pubs-core/2022.0.147/content/NewImages/open-access-icon-orange.png)
Investigating the effect of fusion partners on the enzymatic activity and thermodynamic stability of poly(ethylene terephthalate) degrading enzymes
We investigate the influence of the switchable thermal stability of a fusion partner on the activity of PETases demonstrating a range of optimal reaction temperatures.
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD00067F
Enzyme evolution, engineering and design: mechanism and dynamics: general discussion
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD90022G
Artificial, biomimetic and hybrid enzymes: general discussion
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD90024C
Biocatalytic pathways, cascades, cells and systems: general discussion
Faraday Discuss., 2024, Advance Article
https://doi.org/10.1039/D4FD90023E
About this collection
We are delighted to share with you a selection of the papers associated with a Faraday Discussion on Biocatalysis. More information about the related event may be found here: http://rsc.li/biocatalysis-fd2024. Additional articles will be added to the collection as they are published. The final versions of all the articles presented and a record of the discussions will be published after the event.
Biocatalysis, a rapidly evolving field with increasing impact in synthesis, chemical manufacturing and medicine, is being transformed by advances in biophysical and computational techniques. It is expanding into new areas of chemistry, facilitated by de novo protein design, directed evolution, incorporation of new catalytic functionality into proteins, genetic data, developing spectroscopic and structural techniques, and informed by modelling, machine learning and artificial intelligence. The four themes of this Discussion will unite researchers working in different fields (for example synthetic biology, computational chemistry and mechanistic organic and organometallic chemistry) to improve our understanding of enzyme catalytic power with a view to engineering hybrid and artificial enzymes.
This meeting will cover 4 main themes: Enzyme evolution, engineering and design: mechanism and dynamics, Biocatalytic pathways, cascades, cells and systems, Biocatalysis for industry, medicine and the circular economy, Artificial, biomimetic and hybrid enzymes.
On behalf of the Scientific Committee, we hope you join us and participate in this exciting event, and that you enjoy these articles and the record of the discussion.