Department of Molecular Biology and Ecology of Plants, Tel-Aviv University, Tel-Aviv 6997803, Israel.
Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL, 60439, U.S.A.
Biol Rev Camb Philos Soc. 2015 Nov;90(4):1065-99. doi: 10.1111/brv.12146. Epub 2014 Nov 4.
Proline is not only an essential component of proteins but it also has important roles in adaptation to osmotic and dehydration stresses, redox control, and apoptosis. Here, we review pathways of proline biosynthesis in the three domains of life. Pathway reconstruction from genome data for hundreds of eubacterial and dozens of archaeal and eukaryotic organisms revealed evolutionary conservation and variations of this pathway across different taxa. In the most prevalent pathway of proline synthesis, glutamate is phosphorylated to γ-glutamyl phosphate by γ-glutamyl kinase, reduced to γ-glutamyl semialdehyde by γ-glutamyl phosphate reductase, cyclized spontaneously to Δ(1)-pyrroline-5-carboxylate and reduced to proline by Δ(1)-pyrroline-5-carboxylate reductase. In higher plants and animals the first two steps are catalysed by a bi-functional Δ(1) -pyrroline-5-carboxylate synthase. Alternative pathways of proline formation use the initial steps of the arginine biosynthetic pathway to ornithine, which can be converted to Δ(1)-pyrroline-5-carboxylate by ornithine aminotransferase and then reduced to proline or converted directly to proline by ornithine cyclodeaminase. In some organisms, the latter pathways contribute to or could be fully responsible for the synthesis of proline. The conservation of proline biosynthetic enzymes and significance of specific residues for catalytic activity and allosteric regulation are analysed on the basis of protein structural data, multiple sequence alignments, and mutant studies, providing novel insights into proline biosynthesis in organisms. We also discuss the transcriptional control of the proline biosynthetic genes in bacteria and plants.
脯氨酸不仅是蛋白质的基本组成部分，而且在适应渗透和脱水胁迫、氧化还原控制和细胞凋亡中也具有重要作用。在这里，我们综述了生命三个域中脯氨酸生物合成的途径。从数百个细菌、几十个古菌和真核生物的基因组数据中进行途径重建，揭示了该途径在不同分类群中的进化保守性和变化。在最常见的脯氨酸合成途径中，谷氨酸由γ-谷氨酰激酶磷酸化为γ-谷氨酰磷酸，由γ-谷氨酰磷酸还原酶还原为γ-谷氨酰半醛，自发环化为Δ(1)-吡咯啉-5-羧酸，由Δ(1)-吡咯啉-5-羧酸还原酶还原为脯氨酸。在高等植物和动物中，前两个步骤由双功能的Δ(1)-吡咯啉-5-羧酸合酶催化。脯氨酸形成的替代途径利用精氨酸生物合成途径的初始步骤生成鸟氨酸，鸟氨酸可以通过鸟氨酸转氨酶转化为Δ(1)-吡咯啉-5-羧酸，然后还原为脯氨酸，或者直接由鸟氨酸环化酶转化为脯氨酸。在一些生物体中，后一种途径可能或完全负责脯氨酸的合成。根据蛋白质结构数据、多重序列比对和突变研究，分析了脯氨酸生物合成酶的保守性和催化活性和变构调节的特定残基的重要性，为生物体中的脯氨酸生物合成提供了新的见解。我们还讨论了细菌和植物中脯氨酸生物合成基因的转录控制。
