Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, Campus UAB Bellaterra, Barcelona, Spain.
PLoS One. 2012;7(8):e43775. doi: 10.1371/journal.pone.0043775. Epub 2012 Aug 21.
A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP) by the activity of the enzymes DXP synthase (DXS) and DXP reductoisomerase (DXR). Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway.
甲羟戊酸（MVA）途径对于异戊烯基生物合成以及大肠杆菌和大多数其他细菌的生存是必需的。在该途径的前两步中，通过 DXP 合酶（DXS）和 DXP 还原异构酶（DXR）的活性，MEP 由丙酮酸和甘油醛-3-磷酸等中心代谢中间产物转化为 1-脱氧-D-木酮糖 5-磷酸（DXP）。由于 MVA 途径不存在于人体中，因此它被提议作为开发新型抗生素的有希望的新靶标。然而，人们发现 DXS 或 DXR 的缺失所导致的致死表型可以通过未鉴定的突变以相对较高的效率得到抑制。在这里，我们报告说，相关基因 aceE 和 ribB 中的几个突变可以挽救 DXS 缺陷型突变体的生长，因为编码的酶允许在体内产生足够的 DXP。总的来说，这项工作揭示了细菌中可以进化出多样性的机制，以规避 MVA 途径第一步的阻断。
