 Genome-driven cell engineering in synthetic biology departs from the modularity assumption of DNA-based device construction by focusing on the functioning of whole genomes or whole cells (O’Malley et al. 2008). This practice includes transplantation of foreign or modified genomes into empty ‘chassis cells’ to acquire new functions (Chan et al. 2005), and synthesis of “minimal genomes” (Andrianantoandro et al. 2006; Simons 2021). The notion of a minimal genome highlights the idea that existing organisms may have genomes more complex than necessary for the basic functions of survival and reproduction. The human parasite Mycoplasma genitalium has been considered a model organism for the exploration of such questions due to its small genome, and it has also been the target for the first whole-cell model in systems biology (Karr et al. 2012). In 2010, scientists at the J. Craig Venter Institute (JCVI) created a synthetic genome of another bacterial species of the same genus, Mycoplasma mycoides (Gibson et al. 2010). From the synthetic DNA sequence, the researchers could partly control the production of new Mycoplasma mycoides cells. This genome was further reduced to a working approximation for the simplest synthetic minimal genome (JCVI-syn 3.0), allowing cells to function and reproduce with only 473 genes (Hutchison et al. 2016; see also Sung et al. 2016). At the same time as lower boundaries for biological complexity are explored, other synthetic biologists aim to manipulate and control the functions of genomes of more complex species, such as yeast and algae (Calvert &amp; Frow 2015; Georgianna &amp; Mayfield 2012; see Simons 2021).