Building synthetic chromosomes from natural DNA

• Published in: Nature communications Vol. 14; no. 1; p. 8337
• Main Authors: Coradini, Alessandro L. V., Ville, Christopher Ne, Krieger, Zachary A., Roemer, Joshua, Hull, Cara, Yang, Shawn, Lusk, Daniel T., Ehrenreich, Ian M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.12.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 42; 42/44; 42/70; 45; 45/22; 45/23; 45/41; 45/77; 631/1647/1511; 631/337/103; 631/61/338/552; 64; Artificial chromosomes; Biotechnology; Chromosome deletion; Chromosomes; Chromosomes - genetics; Cloning; Deoxyribonucleic acid; DNA; DNA - genetics; DNA biosynthesis; Humanities and Social Sciences; multidisciplinary; Saccharomyces cerevisiae - genetics; Science; Science (multidisciplinary); Synthesis; Synthetic Biology; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-44112-2

De novo chromosome synthesis is costly and time-consuming, limiting its use in research and biotechnology. Building synthetic chromosomes from natural components is an unexplored alternative with many potential applications. In this paper, we report CReATiNG ( Cl oning, Re programming, and A ssembling Ti led N atural G enomic DNA), a method for constructing synthetic chromosomes from natural components in yeast. CReATiNG entails cloning segments of natural chromosomes and then programmably assembling them into synthetic chromosomes that can replace the native chromosomes in cells. We use CReATiNG to synthetically recombine chromosomes between strains and species, to modify chromosome structure, and to delete many linked, non-adjacent regions totaling 39% of a chromosome. The multiplex deletion experiment reveals that CReATiNG also enables recovery from flaws in synthetic chromosome design via recombination between a synthetic chromosome and its native counterpart. CReATiNG facilitates the application of chromosome synthesis to diverse biological problems. Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.