Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA.
Mol Syst Biol. 2010 Nov 30;6:436. doi: 10.1038/msb.2010.88.
Bacterial genomes encode hundreds to thousands of enzymes, most of which are specialized for particular functions. However, most enzymes have inefficient promiscuous activities, as well, that generally serve no purpose. Promiscuous reactions can be patched together to form multistep metabolic pathways. Mutations that increase expression or activity of enzymes in such serendipitous pathways can elevate flux through the pathway to a physiologically significant level. In this study, we describe the discovery of three serendipitous pathways that allow synthesis of pyridoxal-5'-phosphate (PLP) in a strain of E. coli that lacks 4-phosphoerythronate (4PE) dehydrogenase (PdxB) when one of seven different genes is overexpressed. We have characterized one of these pathways in detail. This pathway diverts material from serine biosynthesis and generates an intermediate in the normal PLP synthesis pathway downstream of the block caused by lack of PdxB. Steps in the pathway are catalyzed by a protein of unknown function, a broad-specificity enzyme whose physiological role is unknown, and a promiscuous activity of an enzyme that normally serves another function. One step in the pathway may be non-enzymatic.
细菌基因组编码数百到数千种酶，其中大多数专门用于特定功能。然而，大多数酶也具有低效的混杂活性，这些活性通常没有任何作用。混杂反应可以组合在一起形成多步代谢途径。增加这些偶然途径中酶的表达或活性的突变可以将途径中的通量提高到生理上显著的水平。在这项研究中，我们描述了三种偶然途径的发现，这些途径允许在缺乏 4-磷酸赤藓糖（4PE）脱氢酶（PdxB）的大肠杆菌菌株中合成吡哆醛-5'-磷酸（PLP），当七种不同基因中的一种过表达时。我们已经详细描述了其中一种途径。该途径使物质从丝氨酸生物合成中分流，并在由于缺乏 PdxB 而导致的正常 PLP 合成途径下游产生中间体。途径中的步骤由一种未知功能的蛋白质、一种广谱酶（其生理作用未知）和一种通常用于其他功能的酶的混杂活性催化。途径中的一个步骤可能是非酶促的。
