Chang C. Liu

Heterologous engineering of receptors using OrthoRep (HERO) for directed evolution of GPCRs in yeast

The paper improves GPCR biosensors in yeast using a new platform called HERO, achieving significant sensitivity gains through directed evolution.

Continuous hypermutation and evolution of noncanonical amino acid synthases

This paper evolves noncanonical amino acid synthases in yeast to produce ncAAs from simple precursors, enabling scalable genetic code expansion.

Continuous hypermutation and evolution of luciferase variants

This paper introduces a streamlined platform for luciferase engineering using continuous hypermutation, resulting in improved light output variants without manual library generation.

BoltzGen: Toward Universal Binder Design

An all-atom diffusion model unifying biomolecular structure prediction and sequence-structure generation designs experimentally validated nanobodies, mini-proteins, and linear or cyclic peptides across 26 diverse targets.

Mapping the evolution of computationally designed protein binders

This paper evolves computationally designed protein binders using in vivo hypermutation and maps their sequence-affinity landscapes to understand affinity improvements and mutation interactions.

A System to Explore the Adaptive Dynamics of Multicopy Plasmids: The Role of Copy Number and Mutation Rate in Evolutionary Outcomes

This study investigates how plasmid copy number and mutation rate affect evolutionary outcomes using the OrthoRep system, finding that low copy number accelerates beneficial allele enrichment while high copy number increases robustness and hitchhiking of deleterious mutations.

Biotin-Independent Saccharomyces cerevisiae with Enhanced Growth: Engineering an Acetyl-CoA Carboxylase Bypass

This paper engineers a biotin-independent Saccharomyces cerevisiae strain by bypassing acetyl-CoA carboxylase, enabling growth without biotin and improved malonate utilization.

Directed evolution of aminoacyl-tRNA synthetases through in vivo hypermutation

This study presents a strategy using OrthoRep to evolve aminoacyl-tRNA synthetases in yeast, resulting in efficient incorporation of non-canonical amino acids into proteins.

Ultra-Efficient Integration of Gene Libraries onto Yeast Cytosolic Plasmids

The paper introduces a method to efficiently integrate gene libraries onto yeast cytosolic plasmids using integrases, enhancing the versatility of OrthoRep for protein engineering.

Continuous evolution of gene libraries towards arbitrary functions reveals the versatility of biomolecular evolution in vivo

This study shows that novel gene functions can emerge rapidly in vivo through continuous evolution under various selection pressures.

Open-ended molecular recording of sequential cellular events into DNA

This paper introduces peCHYRON, a DNA recorder that sequentially records cellular events in mammalian cells using prime editing, enabling durable, high-information, and temporally resolved molecular recording.

Continuous evolution of user-defined genes at 1-million-times the genomic mutation rate

This paper introduces a method to rapidly evolve genes in the lab, revealing new insights into enzyme adaptation that machine learning models cannot predict.

A massively parallel in vivo assay of TdT mutants yields variants with altered nucleotide insertion biases

The paper develops a high-throughput assay to profile and engineer TdT variants, identifying variants with altered nucleotide insertion biases that enhance DNA recording capabilities.

Rapidly inducible yeast surface display for antibody evolution with OrthoRep

This paper introduces an improved AHEAD platform using a synthetic β-estradiol induction system to accelerate antibody evolution in yeast.

Using Continuous Directed Evolution to Improve Enzymes for Plant Applications

The paper describes a method to improve enzymes for plant applications using continuous directed evolution in yeast, demonstrating its effectiveness with a bacterial thiamin synthesis enzyme.

Evolving small-molecule biosensors with improved performance and reprogrammed ligand specificity using OrthoRep

This study uses OrthoRep to evolve biosensors with improved dynamic range and reprogrammed ligand specificity for metabolic pathway engineering.

DNA writing at a single genomic site enables lineage tracing and analog recording in mammalian cells

This paper introduces CHYRON, a DNA recorder that writes new DNA to track lineage and record cellular stimuli, demonstrating its ability to reconstruct lineage relationships and respond to stress signals.

Integrating continuous hypermutation with high-throughput screening for optimization of cis,cis-muconic acid production in yeast

The paper develops a directed evolution workflow combining OrthoRep and a transcription factor-based biosensor to optimize cis,cis-muconic acid production in yeast, achieving >13-fold higher titers.

Scalable, continuous evolution for the generation of diverse enzyme variants encompassing promiscuous activities

This paper develops a continuous directed evolution platform called OrthoRep to generate diverse enzyme variants with promiscuous activities by evolving TmTrpB through multi-mutation pathways.

Potential For Applying Continuous Directed Evolution To Plant Enzymes

The paper discusses two systems for continuous directed evolution of enzymes and tests their adaptation for plant enzyme engineering.

Automated continuous evolution of proteins in vivo

This paper introduces ACE, a platform for automated continuous evolution of proteins in vivo, showing it can achieve desired functions like drug resistance and improved enzyme activity through real-time feedback control.

Scalable continuous evolution of genes at mutation rates above genomic error thresholds

This paper introduces OrthoRep, a system for high-throughput directed evolution of genes in yeast, demonstrating its ability to evolve drug-resistant malarial DHFRs and reveal complex fitness landscapes.