Fitzpatrick Teresa B, Amrhein Nikolaus, Kappes Barbara, Macheroux Peter, Tews Ivo, Raschle Thomas
ETH Zurich, Institute of Plant Sciences, 8092 Zurich, Switzerland.
Biochem J. 2007 Oct 1;407(1):1-13. doi: 10.1042/BJ20070765.
Vitamin B6 is well known in its biochemically active form as pyridoxal 5'-phosphate, an essential cofactor of numerous metabolic enzymes. The vitamin is also implicated in numerous human body functions ranging from modulation of hormone function to its recent discovery as a potent antioxidant. Its de novo biosynthesis occurs only in bacteria, fungi and plants, making it an essential nutrient in the human diet. Despite its paramount importance, its biosynthesis was predominantly investigated in Escherichia coli, where it is synthesized from the condensation of deoxyxylulose 5-phosphate and 4-phosphohydroxy-L-threonine catalysed by the concerted action of PdxA and PdxJ. However, it has now become clear that the majority of organisms capable of producing this vitamin do so via a different route, involving precursors from glycolysis and the pentose phosphate pathway. This alternative pathway is characterized by the presence of two genes, Pdx1 and Pdx2. Their discovery has sparked renewed interest in vitamin B6, and numerous studies have been conducted over the last few years to characterize the new biosynthesis pathway. Indeed, enormous progress has been made in defining the nature of the enzymes involved in both pathways, and important insights have been provided into their mechanisms of action. In the present review, we summarize the recent advances in our knowledge of the biosynthesis of this versatile molecule and compare the two independent routes to the biosynthesis of vitamin B6. Surprisingly, this comparison reveals that the key biosynthetic enzymes of both pathways are, in fact, very similar both structurally and mechanistically.
维生素B6以其生物化学活性形式5'-磷酸吡哆醛而闻名，它是众多代谢酶的必需辅助因子。这种维生素还参与人体的多种功能，从调节激素功能到最近被发现具有强大的抗氧化作用。它的从头生物合成仅发生在细菌、真菌和植物中，这使其成为人类饮食中的必需营养素。尽管其至关重要，但它的生物合成主要是在大肠杆菌中进行研究的，在大肠杆菌中它由脱氧木酮糖5-磷酸和4-磷酸羟基-L-苏氨酸缩合而成，这一过程由PdxA和PdxJ的协同作用催化。然而，现在已经清楚的是，大多数能够产生这种维生素的生物体是通过不同的途径来实现的，该途径涉及糖酵解和磷酸戊糖途径的前体。这条替代途径的特点是存在两个基因，Pdx1和Pdx2。它们的发现引发了对维生素B6的新兴趣，在过去几年中已经进行了大量研究来表征新的生物合成途径。事实上，在确定参与这两条途径的酶的性质方面已经取得了巨大进展，并对它们的作用机制提供了重要见解。在本综述中，我们总结了我们对这种多功能分子生物合成的最新认识进展，并比较了维生素B6生物合成的两条独立途径。令人惊讶的是，这种比较表明，两条途径的关键生物合成酶在结构和机制上实际上非常相似。
