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Genomically minimal cells, such as JCVI-syn3.0 and JCVI-syn3A, offer an empowering framework to study relationships between genotype and phenotype. With a polygenic basis, the fundamental physiological process of cell division depends on multiple genes of known and unknown function in JCVI-syn3A. A physical description of cellular mechanics can further understanding of the contributions of genes to cell division in this genomically minimal context. We review current knowledge on genes in JCVI-syn3A contributing to two physical parameters relevant to cell division, namely, the surface-area-to-volume ratio and membrane curvature. This physical view of JCVI-syn3A may inform the attribution of gene functions and conserved processes in bacterial physiology, as well as whole-cell models and the engineering of synthetic cells.
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Metabolite Damage and Damage Control in a Minimal Genome
ABSTRACT Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and spontaneous side reactions. This extension revealed that several key metabolite damage control systems remain to be identified in JCVI-Syn3A, such as that for methylglyoxal. IMPORTANCE Metabolite damage and repair mechanisms are being increasingly recognized. We present here compelling genetic and biochemical evidence for the universal importance of these mechanisms by demonstrating that stripping a genome down to its barest essentials leaves metabolite damage control systems in place. Furthermore, our metabolomic and cheminformatic results point to the existence of a network of metabolite damage and damage control reactions that extends far beyond the corners of it that have been characterized so far. In sum, there can be little room left to doubt that metabolite damage and the systems that counter it are mainstream metabolic processes that cannot be separated from life itself.
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- PAR ID:
- 10341301
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Editor(s):
- Johnson, Michael David
- Date Published:
- Journal Name:
- mBio
- ISSN:
- 2150-7511
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1128/mbio.01630-22
