Histidine biosynthesis is an ancestral pathway that was assembled before the appearance of the Last Universal Common Ancestor; afterwards, it remained unaltered in all the extant histidine-synthesizing (micro)organisms. It is a metabolic cross-road interconnecting histidine biosynthesis to nitrogen metabolism and the de novo synthesis of purines. This interconnection is due to the reaction catalyzed by the products of hisH and hisF genes. The latter gene is an excellent model to study which trajectories have been followed by primordial cells to build the first metabolic routes, since its evolution is the result of different molecular rearrangement events, i.e. gene duplication, gene fusion, gene elongation, and domain shuffling. Additionally, this review summarizes data concerning the involvement of hisF and its product in other different cellular processes, revealing that HisF very likely plays a role also in cell division control and involvement in virulence and nodule development in different bacteria. From the metabolic viewpoint, these results suggest that HisF plays a central role in cellular metabolism, highlighting the interconnections of different metabolic pathways.

组氨酸的生物合成是一个祖先的途径，是在最后的通用祖先出现之前组装的。此后，它在所有现存的组氨酸合成（微生物）生物中均保持不变。它是将组氨酸生物合成与氮代谢和嘌呤从头合成联系起来的代谢交叉路。这种互连是由于hisH和hisF基因的产物催化的反应。后一个基因是研究原始细胞遵循哪些轨迹建立第一个代谢途径的优秀模型，因为其进化是不同分子重排事件的结果，即基因复制，基因融合，基因延伸和域改组。此外，本综述总结了有关HisF及其产物参与其他不同细胞过程的数据，揭示了HisF很可能在细胞分裂控制中以及在不同细菌的毒力和结节发育中也起作用。从代谢的观点来看，这些结果表明HisF在细胞代谢中起着核心作用，突出了不同代谢途径的相互联系。