Li Bin, Baniasadi Hamid R, Phillips Margaret A, Michael Anthony J
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas TX 75390, U.S.A.
Biochem J. 2025 Jul 22;482(15):BCJ20253210. doi: 10.1042/BCJ20253210.
The polyamine putrescine is synthesized primarily from L-arginine via agmatine in bacteria. There are currently three known routes from agmatine to putrescine, including direct conversion by agmatinase. The other two routes use agmatine deiminase to produce N-carbamoylputrescine from agmatine, then one of two nonhomologous enzymes, putrescine transcarbamylase or N-carbamoylputrescine amidohydrolase (NCPAH), converts N-carbamoylputrescine to putrescine. Here, we functionally identify enzymes from phylogenetically distant bacteria, the ɣ-proteobacterium Shewanella oneidensis, and the actinomycetota species Microterricola gilva, that are novel alternative, nonhomologous, noncanonical NCPAHs that we term AguY, which have emerged by convergent evolution. Kinetic analysis indicates that the AguY enzymes are as efficient as the canonical NCPAH from Pseudomonas aeruginosa in converting N-carbamoylputrescine to putrescine. Genomic evidence suggests that the AguY enzymes may participate in putrescine biosynthetic or agmatine catabolic pathways and are occasionally encoded in genomes that also encode agmatinase. We show that the Type VI secretion system toxin Tse8 from P. aeruginosa has evolved from AguY. It is formally possible that AguY evolved directly or indirectly from the ancient glutamine amidohydrolase GatA, a component of the transamidosome, an RNA/protein complex required for the production of glutamine-charged tRNA. Our study provides a further example of the prevalence of convergent evolution and horizontal gene transfer in polyamine biosynthesis, suggesting pervasive selective pressure to evolve polyamine metabolism in bacteria.
多胺腐胺在细菌中主要由L-精氨酸通过胍丁胺合成。目前已知从胍丁胺到腐胺有三条途径，包括由胍丁胺酶直接转化。另外两条途径是利用胍丁胺脱亚氨酶从胍丁胺产生N-氨甲酰腐胺，然后两种非同源酶之一，腐胺转氨甲酰酶或N-氨甲酰腐胺酰胺水解酶（NCPAH），将N-氨甲酰腐胺转化为腐胺。在这里，我们从系统发育上距离较远的细菌，γ-变形菌希瓦氏菌和放线菌门物种吉尔瓦微小杆菌中功能鉴定出一些酶，它们是新型的、替代性的、非同源的、非典型的NCPAH，我们将其命名为AguY，它们是通过趋同进化产生的。动力学分析表明，AguY酶在将N-氨甲酰腐胺转化为腐胺方面与铜绿假单胞菌的典型NCPAH一样高效。基因组证据表明，AguY酶可能参与腐胺生物合成或胍丁胺分解代谢途径，并且偶尔在也编码胍丁胺酶的基因组中编码。我们表明，铜绿假单胞菌的VI型分泌系统毒素Tse8是由AguY进化而来的。正式来说，AguY有可能直接或间接从古谷氨酰胺酰胺水解酶GatA进化而来，GatA是转氨体的一个组成部分，转氨体是产生谷氨酰胺负载tRNA所需的一种RNA/蛋白质复合物。我们的研究进一步证明了趋同进化和水平基因转移在多胺生物合成中的普遍性，表明细菌中进化多胺代谢存在普遍的选择压力。
