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A back-to-back paper from Alanna Schepartz and @jhdcate.bsky.social groups shows how the E. coli ribosome supports the incorporation of the non-α-amino acid monomers! pubs.acs.org/doi/10.1021/...

Nice work from the Deliz Liang lab @lab-adl.bsky.social on genetically encoding diverse His analogs

Chintan's work demonstrating the efficient incorporation of non-α-amino acid backbones into proteins expressed in both E. coli and mammalian cells just came out! A great collaborative effort from @cgemcci.bsky.social! pubs.acs.org/doi/10.1021/...

We are hiring a postdoc! The group has a funded opening to join our amazing team on the NCI's Frederick, MD campus. This is an opportunity to train in cutting-edge chemical & RNA biology methods with a supportive, tight-knit group. Link to posting below. Please share! jobrxiv.org/job/national...

Engineering the translation apparatus to accept backbone-modified amino acid analogues would enable the programmed synthesis of sequence-defined biopolymers with tunable properties. β-Hydroxy acids ar...

Hepatitis D-like satellite viruses, known as deltaviruses, have been recently discovered in a wide range of animals. These viruses are thought to expr…

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Expanding the genetic code of living cells with noncanonical monomers (ncMs) relies on engineered aminoacyl-tRNA synthetases (aaRS) and their cognate tRNAs. Conventional aaRS engineering strategies rely on translation-dependent selection systems, limiting their utility for ncMs that are poorly accommodated by the native translational machinery. To address this limitation, we recently developed START, a translation-independent platform that selects Methanomethylophilus alvus pyrrolysyl-synthetase (MaPylRS) mutants based on their ability to acylate cognate tRNAMaPyl. START uses barcoded tRNAs to encode the identity of distinct aaRS mutants in a library. Acylation by active aaRS mutants protects the corresponding tRNAs from periodate oxidation, and their identity is retrieved subsequently through sequencing. START was previously applied to genetically encode noncanonical α-amino acids. Here, we successfully applied START to engineer MaPylRS mutants capable of acylating tRNAMaPyl with diverse non-α-amino acid substrates with good efficiency and fidelity, including (R) and (S) enantiomers of a β2-hydroxy acid, a β2-amino acids, and a malonate. Several mutants exhibit notable polyspecificity across noncanonical backbones while maintaining selectivity against their α-amino acid counterparts. Using these novel enzymes, we demonstrate the ribosomal incorporation of both (R)- and (S)-β2-hydroxy acids into a luciferase reporter protein expressed in Escherichia coli with good efficiency and fidelity. These results imply that highly active engineered aaRS/tRNA pairs can overcome the recently established limitations of EF-Tu with respect to non-α-amino acid substrates. The engineered MaPylRS mutants also enabled the successful incorporation of both (R)- and (S)-β2-hydroxy acids into a protein expressed in mammalian cells, demonstrating for the first time that eukaryotic translation can accommodate non-α-backbones.

Our latest work seeks to answer a longstanding question: why is discovering new protein binders seemingly unpredictable – and can we better quantify and understand the de novo binder discover process? 1/12 www.biorxiv.org/content/10.1...

👀 A small polymerase ribozyme that can synthesize itself and its complementary strand! www.science.org/doi/10.1126/...

🚨Our paper is out! 🥳 Hijacking a bacterial ABC transporter for efficient genetic code expansion. Many congrats to everyone involved - a multi-year effort led by @taruniype.bsky.social @maxfottner.bsky.social www.nature.com/articles/s41... it all started years ago with a failed experiment 🧵👇 1/9

Starting 2026 with Quan Pham's paper expanding the chemical toolbox for engineering AAV - New bioorthogonal labeling, including IEDDA, for efficient macromolecule attachment - Incorporation of two different chemistries for dual capsid labeling & much more: onlinelibrary.wiley.com/doi/full/10....

Excited to share our work with Eranthie Weerapana and Tim van Opijnen, co-led by Conor Loynd, Soumya Roy, and Sarah Canarelli! We introduce a new generation of BONCAT tools for the versatile characterization of newly synthesized proteins in pathogenic bacteria. rdcu.be/eI4M5

De novo binder discovery is unpredictable and inefficient due to a lack of quantitative understanding of protein-protein interaction (PPI) sequence-function landscapes. Here, we use our PANCS-Binder t...

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

Bacterial ATP-binding cassette (ABC) transporters can be utilized and engineered to transport non-canonical amino acids into Escherichia coli for highly efficient synthesis of proteins with novel func...

We describe technology to introduce diverse non-natural chemical functionalities site-specifically into the capsid of adeno-associated virus through genetic code expansion, and using them to engineer...

onlinelibrary.wiley.com

Nature Chemical Biology - Engineered aminoacyl-tRNA synthetase (aaRS) mutants have been developed that facilitate ultrafast bioorthogonal noncanonical amino acid tagging (BONCAT) of newly...

They say the sincerest form of flattery is mimicry, and we really love histidine! ❤️ Check out our most recent work on histidine mimics: Genetic incorporation of diverse non-canonical amino acids for histidine substitution. www.biorxiv.org/content/10.1...