Microbial communities are self-controlled by repertoires of lethal agents, the antibiotics. In their turn, these antibiotics are regulated by bioscavengers that are selected in the course of evolution. Kinase-mediated phosphorylation represents one of the general strategies for the emergence of antibiotic resistance. A new subfamily of AmiN-like kinases, isolated from the Siberian bear microbiome, inactivates antibiotic amicoumacin by phosphorylation. The nanomolar substrate affinity defines AmiN as a phosphotransferase with a unique catalytic efficiency proximal to the diffusion limit. Crystallographic analysis and multiscale simulations revealed a catalytically perfect mechanism providing phosphorylation exclusively in the case of a closed active site that counteracts substrate promiscuity. AmiN kinase is a member of the previously unknown subfamily representing the first evidence of a specialized phosphotransferase bioscavenger.

微生物群落由致死剂——抗生素——进行自我控制。反过来，这些抗生素又受进化过程中选择的生物清除剂的调节。激酶介导的磷酸化代表了抗生素耐药性出现的一般策略之一。从西伯利亚熊微生物组中分离出的一种新的 AmiN 样激酶亚家族，通过磷酸化使抗生素阿米库马星失活。纳摩尔底物亲和力将 AmiN 定义为具有接近扩散极限的独特催化效率的磷酸转移酶。晶体学分析和多尺度模拟揭示了一种催化完美的机制，仅在一个封闭的活性位点可以抵消底物混杂的情况下提供磷酸化。