ArticleNature communications2019
Artificial cysteine-lipases with high activity and altered catalytic mechanism created by laboratory evolution.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Computer-Aided Lipase Engineering for Improving Their Stability and Activity in the Food Industry: State of the Art.Molecules (Basel, Switzerland) · 2023Pooled it
- Psyllid Cysteine Cathepsins Directly Cleave the Outer Membrane Protein BamD of Citrus Huanglongbing Pathogen.Plant biotechnology journal · 2026Article
- Effects of Vitamin C Concentration on the Growth and Development of First Instar Juvenile Chinese Horseshoe Crabs (Tachypleus tridentatus) Determined by Transcriptomic and Enzyme Activity Analyses.Marine biotechnology (New York, N.Y.) · 2026Article
- Genetically modified lipases as biocatalysts for diacylglycerol production in the food industry: a critical review.Archives of microbiology · 2025Review
- Enzymatic Hydroesterification of Waste Oils: Combilipase-Assisted Ethyl Ester Synthesis via a Dual-Step Biocatalytic Process.ACS omega · 2025Article
- BioStructNet: Structure-Based Network with Transfer Learning for Predicting Biocatalyst Functions.Journal of chemical theory and computation · 2025Article
- Papain-like cysteine proteases inFrontiers in plant science · 2025Article
- Enhanced Biodiesel Production with Eversa Transform 2.0 Lipase on Magnetic Nanoparticles.Langmuir : the ACS journal of surfaces and colloids · 2024Article
- Biocatalytic Heteroaromatic Amide Formation in Water Enabled by a Catalytic Tetrad and Two Access Tunnels.ACS catalysis · 2024Article
- ALDELE: All-Purpose Deep Learning Toolkits for Predicting the Biocatalytic Activities of Enzymes.Journal of chemical information and modeling · 2024Article
- Prediction of Thermostability of Enzymes Based on the Amino Acid Index (AAindex) Database and Machine Learning.Molecules (Basel, Switzerland) · 2023Article
- Structural Insight into the Catalytic Mechanisms of an L-Sorbosone Dehydrogenase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Structural and biochemical analysis of a novel atypically split intein reveals a conserved histidine specific to cysteine-less inteins.Chemical science · 2023Article
- Ultrahigh-Throughput Directed Evolution of a Metal-Free α/β-Hydrolase with a Cys-His-Asp Triad into an Efficient Phosphotriesterase.Journal of the American Chemical Society · 2023Article
- N-terminal lid swapping contributes to the substrate specificity and activity of thermophilic lipase TrLipE.Frontiers in microbiology · 2023Article
- Cold-Active Lipases and Esterases: A Review on Recombinant Overexpression and Other Essential Issues.International journal of molecular sciences · 2022Review
- An Overview into Polyethylene Terephthalate (PET) Hydrolases and Efforts in Tailoring Enzymes for Improved Plastic Degradation.International journal of molecular sciences · 2022Review
- The Nϵ-Rule for Serine, but Not Cysteine Catalytic Triads.Angewandte Chemie (International ed. in English) · 2022Article
- Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks.International journal of molecular sciences · 2022Review
- Perspectives on the Role of Enzymatic Biocatalysis for the Degradation of Plastic PET.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring enzymes is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing a Ser → Cys exchange at the respective catalytic triads, but this generally induced a breakdown of activity. We now report that this long-standing dogma no longer pertains, provided additional mutations are introduced by directed evolution. By employing Candida antarctica lipase B (CALB) as the model enzyme with the Ser-His-Asp catalytic triad, a highly active cysteine-lipase having a Cys-His-Asp catalytic triad and additional mutations W104V/A281Y/A282Y/V149G can be evolved, showing a 40-fold higher catalytic efficiency than wild-type CALB in the hydrolysis of 4-nitrophenyl benzoate, and tolerating bulky substrates. Crystal structures, kinetics, MD simulations and QM/MM calculations reveal dynamic features and explain all results, including the preference of a two-step mechanism involving the zwitterionic pair Cys105
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.