Remark­able enzyme points the way to redu­cing nitric acid use in industry

Chem­ists at the Uni­ver­sity of War­wick in the UK, in col­lab­or­a­tion with research­ers at Cor­nell Uni­ver­sity in the USA, have repor­ted in the journ­al Nature Chem­ic­al Bio­logy the dis­cov­ery of an enzyme in the bac­teri­um Strep­to­my­ces sca­bies that cata­lyses an aro­mat­ic nitra­tion reac­tion. TxtE, a cyto­chrome P450 enzyme, is the first example of an enzyme that has spe­cific­ally evolved to cata­lyse an aro­mat­ic nitra­tion reac­tion. It does this by using the gases nitro­gen monox­ide, gen­er­ated from the amino acid argin­ine by the nitric oxide syn­thase part­ner enzyme txtD, and dioxy­gen. These res­ults may even­tu­ally find applic­a­tion in indus­tri­al chem­istry, where the highly cor­ros­ive chem­ic­als nitric acid and sul­phur­ic acid are cur­rently used to carry out aro­mat­ic nitra­tion reac­tions. Engin­eer­ing of the TxtE enzyme may allow it to be developed as a nitra­tion biocata­lyst for the pro­duc­tion of indus­tri­al chem­ic­als without the need to use nitric acid. Pro­fess­or Greg Chal­lis of the Depart­ment of Chem­istry at the Uni­ver­sity of War­wick, who led the pro­ject, said: ​“Nitra­tion reac­tions are very import­ant com­mer­cially, for example to make explos­ives and nitroaro­mat­ic com­pounds that are key build­ing blocks for indus­tri­al chem­istry. ​“Such reac­tions are cur­rently per­formed using highly cor­ros­ive chem­ic­als like nitric acid, which is dif­fi­cult to handle and is envir­on­ment­ally unfriendly. It would be very excit­ing if a biocata­lyst could be developed for envir­on­ment­ally-benign indus­tri­al pro­duc­tion of nitroaro­mat­ics ” Cyto­chrome P450 enzymes are ubi­quit­ous in liv­ing organ­isms. Usu­ally they are respons­ible for hydroxyla­tion and oth­er oxid­at­ive reac­tions – but this is the first time that they have been repor­ted to cata­lyse a nitra­tion reac­tion. TxtE cata­lyses the intro­duc­tion of a nitro group into a spe­cif­ic pos­i­tion of the aro­mat­ic ring of the amino acid trypto­phan. This is the first key step in the bio­syn­thes­is of thax­tom­in A. Thax­tom­in A enables Strep­to­my­ces sca­bies to dam­age pota­toes and oth­er root veget­ables by inhib­it­ing cel­lu­lose pro­duc­tion, thereby dam­aging the cell wall and allow­ing an infec­tion to take hold. The enzyme’s cru­cial role in thax­tom­in A bio­syn­thes­is makes it a poten­tial tar­get for the devel­op­ment of new molecules to block thax­tom­in pro­duc­tion and thus pre­vent potato scab, a dis­ease which places a sig­ni­fic­ant eco­nom­ic bur­den on the agri­cul­tur­al industry glob­ally. The paper Cyto­chrome P450 – cata­lyzed L‑tryptophan nitra­tion in thax­tom­in phyto­tox­in bio­syn­thes­iswas pub­lished in the journ­al Nature Chem­ic­al Bio­logy. doi:10.1038/nchembio.1048 Source: Uni­ver­sity of Warwick