title: Minimal genome encoding proteins with constrained amino acid repertoire.
abstract: Minimal bacterial gene set comprises the genetic elements needed for survival of engineered bacterium on a rich medium. This set is estimated to include 300-350 protein-coding genes. One way of simplifying an organism with such a minimal genome even further is to constrain the amino acid content of its proteins. In this study, comparative genomics approaches and the results of gene knockout experiments were used to extrapolate the minimal gene set of mollicutes, and bioinformatics combined with the knowledge-based analysis of the structure-function relationships in these proteins and their orthologs, paralogs and analogs was applied to examine the challenges of completely replacing the rarest residue, cysteine. Among several known functions of cysteine residues, their roles in the active centers of the enzymes responsible for deoxyribonucleoside synthesis and transfer RNA modification appear to be crucial, as no alternative chemistry is known for these reactions. Thus, drastic reduction of the content of the rarest amino acid in a minimal proteome appears to be possible, but its complete elimination is challenging.
authors.affiliation: A.A.Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny per. 19, Moscow, 127994, Russia, Faculty of Bioengineering and Bioinformatics, Moscow State University, Vorobievy Gory 1-73, Moscow 119992, Russia, Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO 64110, USA, École Polytechnique, Palaiseau Cedex, 91128, France, O'Reilly Science Art, LLC, P.O. Box 416 Cardiff, CA 92007, USA and Department of Microbiology, Molecular Genetics and Immunology, Kansas University Medical Center, Kansas City, KS 66160, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Tsoy
authors.forename: Marina
authors.initials: M
authors.lastname: Yurieva
authors.forename: Andrey
authors.initials: A
authors.lastname: Kucharavy
authors.forename: Mary
authors.initials: M
authors.lastname: O'Reilly
authors.forename: Arcady
authors.initials: A
authors.lastname: Mushegian
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D003545:Cysteine / Q000032:analysis / Q000737:chemistry*; D005818:Genetic Engineering; D016680:Genome, Bacterial; D045704:Mycoplasma genitalium / Q000235:genetics*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D003545:Cysteine