Essential metabolism for a minimal cell

Essential metabolism for a minimal cell
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DOI:
10.7554/elife.36842
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发表时间:
2019-01-18
期刊:
影响因子:
7.7
通讯作者:
Luthey-Schulten, Zaida
Luthey-Schulten, Zaida
中科院分区:
生物学1区
文献类型:
--
作者:
Breuer, Marian;Earnest, Tyler M.;Luthey-Schulten, Zaida

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JCVI-SYN3A是一种具有543 KBP基因组和493个基因的强大最小细胞,为研究生命的基础知识提供了一种多功能平台。使用其前体上可用的大量实验信息,Mycoplasma mycoides Capri,我们组装了一个近乎完整的代谢网络,其中98%的酶促反应由注释或实验支持。该模型与体内转座子诱变实验的基因组规模非常吻合,显示Matthews相关系数为0.59。重建中的基因的体内本质性或准语言性高92%(68%必不可少),而硅质的必要性为79%。 JCVI-SYN3A中最小代谢的这种连贯的模型同时也指出了有关JCVI-SYN3A,Whicsynthetic mycoplasma mycoides jcvi-syn1.0 Clone Smmycp235-1的最低基因组,whicsynththetic mycoplasma mycoides jcvi-syn1.0 clone smmycp235-1,完整的基因,通用或完全不清楚的功能。特别是,该模型与体内本质性和蛋白质组学数据的比较产生了有关基因功能和代谢能力的特定假设。并为进一步的基因删除提供建议。这样,模型及其随附的数据指导了对最小单元的未来研究。最后,对具有不清功能的30个基本基因的鉴定将激发人们对新陈代谢以外的新生物学机制的搜索。
JCVI-syn3A, a robust minimal cell with a 543 kbp genome and 493 genes, provides a versatile platform to study the basics of life. Using the vast amount of experimental information available on its precursor, Mycoplasma mycoides capri, we assembled a near-complete metabolic network with 98% of enzymatic reactions supported by annotation or experiment. The model agrees well with genome-scale in vivo transposon mutagenesis experiments, showing a Matthews correlation coefficient of 0.59. The genes in the reconstruction have a high in vivo essentiality or quasi-essentiality of 92% (68% essential), compared to 79% in silico essentiality. This coherent model of the minimal metabolism in JCVI-syn3A at the same time also points toward specific open questions regarding the minimal genome of JCVI-syn3A, whicSynthetic Mycoplasma mycoides JCVI-syn1.0 clone sMmYCp235-1, complete sequenceh still contains many genes of generic or completely unclear function. In particular, the model, its comparison to in vivo essentiality and proteomics data yield specific hypotheses on gene functions and metabolic capabilities; and provide suggestions for several further gene removals. In this way, the model and its accompanying data guide future investigations of the minimal cell. Finally, the identification of 30 essential genes with unclear function will motivate the search for new biological mechanisms beyond metabolism.