ArticleNature chemistry2023
Activity-based directed evolution of a membrane editor in mammalian cells.
Article in Nature chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Phospholipases D: An Update on Structure-Function Relationships.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- How to catch a lipid transporter.Nature chemical biology · 2026Article
- Membrane editing with proximity labeling reveals regulators of lipid homeostasis.Nature chemical biology · 2026Article
- Selective Editing and Functionalization of the Mammalian Lipidome.bioRxiv : the preprint server for biology · 2026Article
- Chemical biology approaches for revealing interorganelle lipid transport pathways.Current opinion in cell biology · 2026Review
- Riboswitch-controlled lipid conversion enables functional membrane asymmetry in artificial cells.Communications biology · 2026Article
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.bioRxiv : the preprint server for biology · 2025Article
- Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.Annual review of biochemistry · 2025Review
- Synthetic Lipid Biology.Chemical reviews · 2025Review
- The dynamic regulatory network of phosphatidic acid metabolism: a spotlight on substrate cycling between phosphatidic acid and diacylglycerol.Biochemical Society transactions · 2024Review
- A phosphorylation-controlled switch confers cell cycle-dependent protein relocalization.Nature cell biology · 2024Article
- Optogenetic Strategies for Optimizing the Performance of Phospholipids Biosensors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Imaging Interorganelle Phospholipid Transport by Extended Synaptotagmins Using Bioorthogonally Tagged Lipids.ACS chemical biology · 2024Article
- A phosphorylation-controlled switch confers cell cycle-dependent protein relocalization.bioRxiv : the preprint server for biology · 2024Article
- Super-Resolution Imaging of Clickable Lipids With Lipid Expansion Microscopy (LExM).Current protocols · 2024Article
- "Blue Light, Camera, Action!"ACS central science · 2024Article
- Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling.ACS central science · 2024Article
- Chemical Approaches for Measuring and Manipulating Lipids at the Organelle Level.Cold Spring Harbor perspectives in biology · 2023Review
- Virus-assisted directed evolution of biomolecules.Current opinion in chemical biology · 2023Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cellular membranes contain numerous lipid species, and efforts to understand the biological functions of individual lipids have been stymied by a lack of approaches for controlled modulation of membrane composition in situ. Here we present a strategy for editing phospholipids, the most abundant lipids in biological membranes. Our membrane editor is based on a bacterial phospholipase D (PLD), which exchanges phospholipid head groups through hydrolysis or transphosphatidylation of phosphatidylcholine with water or exogenous alcohols. Exploiting activity-dependent directed enzyme evolution in mammalian cells, we have developed and structurally characterized a family of 'superPLDs' with up to a 100-fold enhancement in intracellular activity. We demonstrate the utility of superPLDs for both optogenetics-enabled editing of phospholipids within specific organelle membranes in live cells and biocatalytic synthesis of natural and unnatural designer phospholipids in vitro. Beyond the superPLDs, activity-based directed enzyme evolution in mammalian cells is a generalizable approach to engineer additional chemoenzymatic biomolecule editors.
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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.