National University of Singapore engineers LySE for near-continuous bacterial gene cluster evolution
Updated
Updated · Nature.com · May 1
National University of Singapore engineers LySE for near-continuous bacterial gene cluster evolution
3 articles · Updated · Nature.com · May 1
The T7 phage-based system achieved mutation rates of 3.82×10−5 per base and improved a PET-monomer metabolism strain’s endpoint biomass by 50.9% in five cycles.
LySE alternates lysis and transduction in E. coli, preserving discrete checkpoints while discarding off-target genomic mutations and enabling evolution of large gene clusters up to about 40 kilobases.
Researchers said the method could broaden directed evolution for metabolic pathways, protein complexes and recycling-related biotechnologies by combining continuous-system speed with greater experimental control and accessibility.
Could LySE's breakthrough in controlled, rapid evolution unlock new cures or create unforeseen risks in fighting antibiotic resistance?
How might evolving large gene clusters with LySE reshape efforts to tackle plastic pollution or design next-generation biomanufacturing?
What safeguards exist to ensure LySE-evolved bacteria don't escape labs or disrupt natural microbial ecosystems?
NUS LySE Breakthrough: Rapid Directed Evolution of Large Gene Clusters Achieves 50.9% Increased Plastic Upcycling Efficiency
Overview
In April 2025, the National University of Singapore introduced LySE, a novel system that uses an engineered T7 phage and a hypermutagenic DNA polymerase to rapidly evolve large gene clusters up to 39 kilobases. LySE operates through cycles of bacterial lysis and phage transduction, which eliminate unwanted mutations in the host genome and focus evolution on the target genes. This approach enabled a 50.9% increase in E. coli biomass using ethylene glycol and a 25-fold rise in antibiotic resistance within just five cycles. These breakthroughs highlight LySE's potential for plastic waste bioremediation and antibiotic resistance research, while future efforts aim to enhance safety, ethical governance, and expand its host range beyond E. coli.