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      Towards synthesis of a minimal cell

      review-article
      1 , a , 2 , b
      Molecular Systems Biology
      cell, genome, minimal, RNA, self-replication, translation

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          Abstract

          Construction of a chemical system capable of replication and evolution, fed only by small molecule nutrients, is now conceivable. This could be achieved by stepwise integration of decades of work on the reconstitution of DNA, RNA and protein syntheses from pure components. Such a minimal cell project would initially define the components sufficient for each subsystem, allow detailed kinetic analyses and lead to improved in vitro methods for synthesis of biopolymers, therapeutics and biosensors. Completion would yield a functionally and structurally understood self-replicating biosystem. Safety concerns for synthetic life will be alleviated by extreme dependence on elaborate laboratory reagents and conditions for viability. Our proposed minimal genome is 113 kbp long and contains 151 genes. We detail building blocks already in place and major hurdles to overcome for completion.

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          Most cited references53

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          Essential genes of a minimal bacterium.

          Mycoplasma genitalium has the smallest genome of any organism that can be grown in pure culture. It has a minimal metabolism and little genomic redundancy. Consequently, its genome is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. Using global transposon mutagenesis, we isolated and characterized gene disruption mutants for 100 different nonessential protein-coding genes. None of the 43 RNA-coding genes were disrupted. Herein, we identify 382 of the 482 M. genitalium protein-coding genes as essential, plus five sets of disrupted genes that encode proteins with potentially redundant essential functions, such as phosphate transport. Genes encoding proteins of unknown function constitute 28% of the essential protein-coding genes set. Disruption of some genes accelerated M. genitalium growth.
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            Universal rules and idiosyncratic features in tRNA identity.

            Correct expression of the genetic code at translation is directly correlated with tRNA identity. This survey describes the molecular signals in tRNAs that trigger specific aminoacylations. For most tRNAs, determinants are located at the two distal extremities: the anticodon loop and the amino acid accepting stem. In a few tRNAs, however, major identity signals are found in the core of the molecule. Identity elements have different strengths, often depend more on k cat effects than on K m effects and exhibit additive, cooperative or anti-cooperative interplay. Most determinants are in direct contact with cognate synthetases, and chemical groups on bases or ribose moieties that make functional interactions have been identified in several systems. Major determinants are conserved in evolution; however, the mechanisms by which they are expressed are species dependent. Recent studies show that alternate identity sets can be recognized by a single synthetase, and emphasize the importance of tRNA architecture and anti-determinants preventing false recognition. Identity rules apply to tRNA-like molecules and to minimalist tRNAs. Knowledge of these rules allows the manipulation of identity elements and engineering of tRNAs with switched, altered or multiple specificities.
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              Use of T7 RNA polymerase to direct expression of cloned genes.

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                Author and article information

                Journal
                Mol Syst Biol
                Molecular Systems Biology
                1744-4292
                2006
                22 August 2006
                : 2
                : 45
                Affiliations
                [1 ]Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, USA
                [2 ]Department of Genetics, Harvard Medical School, Boston, MA, USA
                Author notes
                [a ]Department of Pharmacology, Vanderbilt University Medical Center, 23rd Ave.S. at Pierce, Nashville, TN 37232, USA. Tel.: +1 615 936 3112; Fax: +1 615 936 5555; E-mail: a.forster@ 123456vanderbilt.edu
                [b ]Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, NBR 238, Boston, MA 02115, USA. Tel.: +1 617 432 1278; Fax: +1 617 432 6513
                Article
                msb4100090
                10.1038/msb4100090
                1681520
                16924266
                353f9f36-7801-4ee5-a8ae-6f5dd29cc2f7
                Copyright © 2006, EMBO and Nature Publishing Group
                History
                : 7 May 2006
                : 26 July 2006
                Page count
                Pages: 1
                Categories
                Review Article

                Quantitative & Systems biology
                minimal,self-replication,rna,translation,genome,cell
                Quantitative & Systems biology
                minimal, self-replication, rna, translation, genome, cell

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