A family of archaeal hibernation factors that bind in tandem and protect ribosomes in dormant cells - Nature Communications

Hibernation factors preserve ribosomes during cellular dormancy. Here, the authors identify a family of archaeal hibernation factors and use genetic, biochemical, and structural studies to show how th...

nature.com

Altering the ribosome exit tunnel to improve consecutive incorporation of challenging monomers

Ribosomes are capable of incorporating a wide array of natural and unnatural monomers into growing polymer chains, but can be stalled by monomers with constrained or non-natural backbones. Here we eva...

biorxiv.org

C-GEM welcomes sixth cohort of summer undergraduates, Center for Genetically Encoded Materials

Welcome to the 2026 cohort of Summer Undergraduate Research Program (SURP) scholars! This year, we are hosting four scholars across UC Berkeley, Cornell...

gem-net.net

Bioinformatics-Guided Discovery of a Thermostable and Highly Promiscuous RiPP Cyclodehydratase | ChemRxiv

Ribosomally synthesized and post-translationally modified peptides (RiPPs) often contain backbone-embedded oxazoline/thiazoline heterocycles that are installed by enzymes known as cyclodehydratases. These enzymes are of great interest as biocatalysts for ...

chemrxiv.org

Backbone Sensitivity - Cate & Schepartz Groups

Researchers in the Cate and Schepartz Groups at the University of California, Berkeley, and the Lawrence Berkeley National Laboratory, published in the <em>Journal of the American Chemical Society</em...

americanpeptidesociety.org

Co-Translational Incorporation of (R)- and (S)-β2-Hydroxyacids In Vivo: Directed Evolution of Efficient Aminoacyl-tRNA Synthetases

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.

pubs.acs.org

Site-selective protein editing by backbone extension acyl rearrangements - Nature Chemical Biology

A post-translational backbone extension acyl rearrangement (BEAR) reaction has now been developed that converts a ribosomal protein product into a new product containing a β-peptide, γ-peptide or δ-pe...

nature.com

An archaeal genetic code with all TAG codons as pyrrolysine

Multiple genetic codes developed during the evolution of eukaryotes and bacteria, yet no alternative genetic code is known for archaea. We used proteomics to confirm our prediction that certain archae...

science.org

Home - Bay Area Science Festival

Bring the whole family to experience 100+ jaw-dropping demonstrations, hands-on experiments, astounding games, behind the scenes lab tours, film screenings

bayareasciencefestival.org

NSF Graduate Research Fellowship Program (GRFP)

nsf.gov

Chemical and ribosomal synthesis of atropisomeric and macrocyclic peptides with embedded quinolines - Nature Chemistry

Expanding the complexity of genetically encoded peptides is a long-standing challenge at the intersection of chemistry and biology. Now it has been shown that linear peptides with a reactive N-termina...

nature.com

Managing Director, NSF Center for the Mechanical Control of Chemistry

Job TitleManaging Director, NSF Center for the Mechanical Control of Chemistry Agency Texas A&amp;M University Department Chemistry Proposed Minimum SalaryCommensurate Job LocationCollege Station, Tex...

tamus.wd1.myworkdayjobs.com

Site-selective protein editing by backbone extension acyl rearrangements - Nature Chemical Biology

A post-translational backbone extension acyl rearrangement (BEAR) reaction has now been developed that converts a ribosomal protein product into a new product containing a β-peptide, γ-peptide or δ-pe...

nature.com

Site-selective protein editing by backbone extension acyl rearrangements - Nature Chemical Biology

A post-translational backbone extension acyl rearrangement (BEAR) reaction has now been developed that converts a ribosomal protein product into a new product containing a β-peptide, γ-peptide or δ-pe...

nature.com

NSF commits $15 million to renewed funding for the Center for Genetically Encoded Materials | College of Chemistry

chemistry.berkeley.edu

Learn about Directed Evolution Through Play, Center for Genetically Encoded Materials

C-GEM transformed the Nobel Prize-winning technique of directed evolution into an educational board game! Directed Evolution: The Game tasks players with...

gem-net.net

Further Confirmation of the Structure of 3′-(2-Pyridyldithio)-3′-deoxyadenosine and 3′-Thio-3′-deoxyadenosine: Synthetic Convergence with Cordycepin

3′-Deoxynucleosides have demonstrated profound biochemical utility, including in our recent work on the use of aminoacyl thio-tRNAs for in vitro translation. Though our preparation of 3′-(2-pyridyldithio)-3′-deoxyadenosine─a key synthetic precursor en route to aminoacyl thio-tRNAs─followed robust prior precedents, an unrelated recent structural revision prompted us to validate the regioselectivity of our route further. Here we provide confirmatory evidence for the structure of 3′-(2-pyridyldithio)-3′-deoxyadenosine and downstream analogues via synthetic convergence with a 3′-deoxynucleoside antibiotic, cordycepin, and concomitant MicroED analysis.

pubs.acs.org

Escherichia coli ribosomes support translation of (R) and (S) β2-hydroxyacids in vitro: a structural and biochemical study

The ribosomal incorporation of backbone-modified amino acid analogs into peptides and proteins enables the programmed synthesis of sequence-defined biopolymers with tunable properties. However, the su...

chemrxiv.org

Monitoring monomer-specific acyl–tRNA levels in cells with PARTI

Abstract. We describe a new assay that reports directly on the acylation state of a user-chosen transfer RNA (tRNA) in cells. We call this assay 3-Prime Ad

academic.oup.com