JCVI-Syn3A / JCVI-Syn3B
JCVI-Syn3A and JCVI-Syn3B are genomically minimal cells derived from [[mycoplasma-mycoides|Mycoplasma mycoides]] subsp. capri str. GM12 by systematic genome reduction at the J. Craig Venter Institute. They retain only essential or quasi-essential genes and represent the simplest known self-replicating organisms.
Genome and Design
- JCVI-Syn3.0: the original minimal cell with the smallest genome (473 genes), but exhibited pleomorphism and irregular cell division.
- JCVI-Syn3A: Syn3.0 plus 19 additional genes restoring regular spherical morphology and cell division (~493 genes, 543 kbp). Used for the whole-cell kinetic model (Thornburg et al., 2022, Cell) and lipidome minimization experiments (Justice et al., 2024, Nature Communications).
- JCVI-Syn3B: a near-identical variant used for lipidome adaptation studies (Safronova et al., 2024, Cell Reports; Safronova et al., 2024, bioRxiv; Oertel et al., 2025, bioRxiv).
As a Membrane Model System
Minimal cells are ideal for studying lipidome design principles because:
- They have a single plasma membrane (no cell wall, no outer membrane) — what you measure is what you get.
- They have minimal lipid biosynthetic capacity, relying on lipids from growth media. This enables experimental control of lipidome composition through lipid diets.
- Their small genomes make comprehensive characterization and modeling feasible.
Key Findings from Our Work
- A two-component lipidome (cholesterol + one phospholipid) supports life in Syn3A (Justice et al., 2024, Nature Communications).
- Syn3B exhibits lipidome flexibility in response to temperature, but with impaired head-group-specific acyl chain remodeling compared to M. mycoides — associated with impaired homeoviscous adaptation (Safronova et al., 2024, Cell Reports).
- Lipidome diversity enhances robustness to osmotic stress and correlates with maximal growth rate (Safronova et al., 2024, bioRxiv; Oertel et al., 2025, bioRxiv).
- Cyclodextrin-mediated lipid diets produce lipidomes with 7 to ~30 species, enabling systematic exploration of lipidome complexity (Safronova et al., 2024, bioRxiv).