Autocatalytic selection of gene functions in synthetic cells
Abstract
The integration of biological functions into a single operating system is considered a major challenge in the construction of a synthetic cell. We present autocatalytic selection (ACS) of gene functions as a driver for integrating biological modules in vitro. A gene of interest (GOI) is introduced into a minimal DNA self-replicator and the function of the GOI is linked to transcription, translation or DNA replication through a positive feedback loop. As the encoded function eventually promotes DNA self-replication, the gene variants with greater activity are selected. Using different coupling mechanisms, we demonstrate ACS of three functions: transcription, in situ regeneration of dGTP from dGMP to support DNA replication, and β-galactosidase activity. The latter example illustrates how a function that is not directly related to the Central Dogma can be selected. In addition, we show that metabolically active replicators can be enriched from a library of variants generated by random mutagenesis. This work paves the way for ACS-driven Darwinian evolution of virtually any biomolecule in vitro, streamlining the construction of increasingly complex synthetic cells as well as the engineering of biotechnologically relevant enzymes.
Related
- Plug-and-Play or Plug-and-Pray? Impact of random versus targeted integration on the linearity and orthogonality of synthetic gene circuits in CHO cells.
- A modular synthetic promoter toolkit for programmable gene control in activated and chronically stimulated T cells.
- A data-driven modeling framework for mapping genotypes to synthetic microbial community functions
- Decoding gene responsiveness to synthetic chromatin reader-actuators with multi-modal epigenomic profiling.
- Alzheimer’s disease diagnosis based on gene selection and cross-tissue validation
BibTeX
@article{heras2026autocatalytic,
title = {{Autocatalytic selection of gene functions in synthetic cells}},
author = {Laura Sierra Heras and Christophe Danelon},
journal = {Communications Biology},
year = {2026},
month = may,
doi = {10.1038/s42003-026-10372-z},
url = {https://hal.inrae.fr/hal-05799798v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Autocatalytic selection of gene functions in synthetic cells
AU - Laura Sierra Heras
AU - Christophe Danelon
PY - 2026
DA - 2026/05/27
JO - Communications Biology
DO - 10.1038/s42003-026-10372-z
UR - https://hal.inrae.fr/hal-05799798v1
AB - The integration of biological functions into a single operating system is considered a major challenge in the construction of a synthetic cell. We present autocatalytic selection (ACS) of gene functions as a driver for integrating biological modules in vitro. A gene of interest (GOI) is introduced into a minimal DNA self-replicator and the function of the GOI is linked to transcription, translation or DNA replication through a positive feedback loop. As the encoded function eventually promotes DNA self-replication, the gene variants with greater activity are selected. Using different coupling mechanisms, we demonstrate ACS of three functions: transcription, in situ regeneration of dGTP from dGMP to support DNA replication, and β-galactosidase activity. The latter example illustrates how a function that is not directly related to the Central Dogma can be selected. In addition, we show that metabolically active replicators can be enriched from a library of variants generated by random mutagenesis. This work paves the way for ACS-driven Darwinian evolution of virtually any biomolecule in vitro, streamlining the construction of increasingly complex synthetic cells as well as the engineering of biotechnologically relevant enzymes.
SN - 2399-3642
ER -