ETH Zurich, Institute of Microbiology, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Chem Commun (Camb). 2021 Mar 11;57(20):2441-2463. doi: 10.1039/d0cc08078k. Epub 2021 Feb 19.
Chorismate and isochorismate represent an important branching point connecting primary and secondary metabolism in bacteria, fungi, archaea and plants. Chorismate- and isochorismate-converting enzymes are potential targets for new bioactive compounds, as well as valuable biocatalysts for the in vivo and in vitro synthesis of fine chemicals. The diversity of the products of chorismate- and isochorismate-converting enzymes is reflected in the enzymatic three-dimensional structures and molecular mechanisms. Due to the high reactivity of chorismate and its derivatives, these enzymes have evolved to be accurately tailored to their respective reaction; at the same time, many of them exhibit a fascinating flexibility regarding side reactions and acceptance of alternative substrates. Here, we give an overview of the different (sub)families of chorismate- and isochorismate-converting enzymes, their molecular mechanisms, and three-dimensional structures. In addition, we highlight important results of mutagenetic approaches that generate a broader understanding of the influence of distinct active site residues for product formation and the conversion of one subfamily into another. Based on this, we discuss to what extent the recent advances in the field might influence the general mechanistic understanding of chorismate- and isochorismate-converting enzymes. Recent discoveries of new chorismate-derived products and pathways, as well as biocatalytic conversions of non-physiological substrates, highlight how this vast field is expected to continue developing in the future.
分支酸和异分支酸代表了细菌、真菌、古菌和植物中连接初级和次级代谢的重要分支点。分支酸和异分支酸转化酶是新生物活性化合物的潜在靶点，也是体内和体外合成精细化学品的有价值的生物催化剂。分支酸和异分支酸转化酶产物的多样性反映在酶的三维结构和分子机制中。由于分支酸及其衍生物的高反应性，这些酶已经进化到能够精确地适应各自的反应；同时，它们中的许多酶在侧反应和接受替代底物方面表现出令人着迷的灵活性。在这里，我们概述了不同的（亚）家族的分支酸和异分支酸转化酶，它们的分子机制和三维结构。此外，我们还强调了诱变方法的重要结果，这些结果更深入地了解了不同活性位点残基对产物形成和一个亚家族转化为另一个亚家族的影响。在此基础上，我们讨论了该领域的最新进展在多大程度上可能影响对分支酸和异分支酸转化酶的一般机制理解。新发现的分支酸衍生产物和途径，以及非生理底物的生物催化转化，强调了这个广阔领域在未来将如何继续发展。
