Pyridoxal 5'-phosphate synthesis and salvage in Bacteria and Archaea: predicting pathway variant distributions and holes.
Pyridoxal 5'-phosphate synthesis and salvage in Bacteria and Archaea: predicting pathway variant distributions and holes.
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DOI：
10.1099/mgen.0.000926
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发表时间：
2023-03
影响因子：
3.9
通讯作者：
de Crecy-Lagard, Valerie
中科院分区：
文献类型：
--
作者：
Denise, Remi;Babor, Jill;Gerlt, John A.;de Crecy-Lagard, Valerie
吡哆醛5 '-磷酸或PLP是一种辅助因子，来源于B6维生素，对所有已知生物的生长至关重要。PLP合成和补救途径在一些模式物种中得到了很好的表征，尽管关键组分，如维生素B6转运蛋白，在包括模式细菌在内的许多生物体中仍有待鉴定 大肠杆菌 或 枯草芽孢杆菌。使用比较基因组方法，PLP的合成和补救途径进行了预测，在5840细菌和古细菌物种与完整的基因组。在此过程中，调查了两个已知的从头生物合成途径和以前确定的非正交位移的情况下的分布。该分析显示，在许多生物体中仍有几个PLP从头途径基因有待鉴定，这要么是因为单独的序列相似性不能用于区分几个同源候选基因，要么是由于非正交置换。使用已发表的TnSeq数据鉴定了这些通路孔中的一些的候选者，但仍有许多。我们发现约10%的分析生物依赖于补救，但需要进一步分析以确定潜在的转运蛋白。 这项工作是模拟社区中B6维生素交换的起点，预测给定生物体对靶向PLP合成酶的药物的敏感性，并确定未来几年需要解决的许多知识空白。
Pyridoxal 5’-phosphate or PLP is a cofactor derived from B6 vitamers and essential for growth in all known organisms. PLP synthesis and salvage pathways are well characterized in a few model species even though key components, such as the vitamin B6 transporters, are still to be identified in many organisms including the model bacteria Escherichia coli or Bacillus subtilis . Using a comparative genomic approach, PLP synthesis and salvage pathways were predicted in 5840 bacterial and archaeal species with complete genomes. The distribution of the two known de novo biosynthesis pathways and previously identified cases of non-orthologous displacements were surveyed in the process. This analysis revealed that several PLP de novo pathway genes remain to be identified in many organisms, either because sequence similarity alone cannot be used to discriminate among several homologous candidates or due to non-orthologous displacements. Candidates for some of these pathway holes were identified using published TnSeq data, but many remain. We find that ~10 % of the analysed organisms rely on salvage but further analyses will be required to identify potential transporters. This work is a starting point to model the exchanges of B6 vitamers in communities, predict the sensitivity of a given organism to drugs targeting PLP synthesis enzymes, and identify numerous gaps in knowledge that will need to be tackled in the years to come.
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影响因子：
14.9
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/j.jbc.2021.101046
发表时间：
2021-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Pan C;Zimmer A;Shah M;Huynh MS;Lai CC;Sit B;Hooda Y;Curran DM;Moraes TF
通讯作者：
Moraes TF