近日，上海交通大学生命科学技术学院教授许平团队在微生物分解代谢研究领域获得突破，进一步阐明尼古丁等环境毒物的降解机制。日前，相关研究成果以封面论文形式发表于《分子微生物学》。

在烟草加工过程中会产生大量富含尼古丁等烟碱类化合物的固体和液体废弃物，这些物质易进入地下水，并对环境造成一定的影响，因此降低烟草废弃物中尼古丁含量对于保护环境有着重要的意义。

恶臭假单胞菌S16能够以尼古丁作为底物生长并将其完全矿化，在降低烟草中尼古丁含量和处理烟草废物的过程中发挥重要作用。课题组成员通过研究假单胞菌属中参与重要环境毒物尼古丁分解代谢的一个新的调控蛋白的结合方式，并在此基础上提出一种新型调控蛋白结合DNA模型。

此外，尼古丁微生物分解代谢途径中还存在许多具有重要生物化学研究价值和化学催化应用价值的酶。研究团队成功解析了两种酶的晶体结构，通过酶活性动力学检测、计算机分子对接模拟、量子化学计算，该团队揭示了这种水解酶有着针对各自底物量身定制的活性位点结构，从而不能互相交换酰胺底物进行交叉水解反应的特殊巧妙的分子机制。（来源：中国科学报 黄辛）

Structural insights into the specific recognition of N-heterocycle biodenitrogenation-derived substrates by microbial amide hydrolases

Summary  N-heterocyclic compounds from industrial wastes, including nicotine, are environmental pollutants or toxicants responsible for a variety of health problems. Microbial biodegradation is an attractive strategy for the removal of N-heterocyclic pollutants, during which carbon–nitrogen bonds in N-heterocycles are converted to amide bonds and subsequently severed by amide hydrolases. Previous studies have failed to clarify the molecular mechanism through which amide hydrolases selectively recognize diverse amide substrates and complete the biodenitrogenation process. In this study, structural, computational and enzymatic analyses showed how the N-formylmaleamate deformylase Nfo and the maleamate amidase Ami, two pivotal amide hydrolases in the nicotine catabolic pathway of Pseudomonas putida S16, specifically recognize their respective substrates. In addition, comparison of the α-β-α groups of amidases, which include Ami, pinpointed several subgroup-characteristic residues differentiating the two classes of amide substrates as containing either carboxylate groups or aromatic rings. Furthermore, this study reveals the molecular mechanism through which the specially tailored active sites of deformylases and amidases selectively recognize their unique substrates. Our work thus provides a thorough elucidation of the molecular mechanism through which amide hydrolases accomplish substrate-specific recognition in the microbial N-heterocycles biodenitrogenation

原文链接：http://onlinelibrary.wiley.com/doi/10.1111/mmi.12511/pdf