Chun Stephanie W, Narayan Alison R H
Department of Chemistry, University of Michigan, 930 North University Ave, Ann Arbor, MI 48109-1055, USA.
Life Sciences Institute, University of Michigan, 210 Washtenaw Ave, Ann Arbor, MI 48109-2216, USA.
Synlett. 2019 Jul;30(11):1269-1274. doi: 10.1055/s-0037-1611755. Epub 2019 Mar 19.
Stereospecific generation of α-amino ketones from common α-amino acids is difficult to achieve, often employing superstoichiometric alkylating reagents and requiring multiple protecting group manipulations. In contrast, the α-oxoamine synthase protein family performs this transformation stereospecifically in a single step without the need for protecting groups. Herein, we detail the characterization of the 8-amino-7-oxononanoate synthase (AONS) domain of the four-domain polyketide-like synthase SxtA, which natively mediates the formation of the ethyl ketone derivative of arginine. The function of each of the four domains is elucidated, leading to a revised proposal for the initiation of saxitoxin biosynthesis, a potent neurotoxin. We also demonstrate the synthetic potential of SxtA AONS, which is applied to the synthesis of a panel of novel α-amino ketones.
从常见的α-氨基酸立体定向生成α-氨基酮很难实现，通常需要使用超化学计量的烷基化试剂，并且需要进行多次保护基操作。相比之下，α-氧代胺合酶蛋白家族可在一步反应中立体定向地进行这种转化，而无需保护基。在此，我们详细描述了四结构域聚酮化合物样合酶SxtA的8-氨基-7-氧代壬酸合酶（AONS）结构域的特征，该结构域天然介导精氨酸乙基酮衍生物的形成。阐明了四个结构域各自的功能，从而对强力神经毒素石房蛤毒素生物合成的起始提出了修订建议。我们还展示了SxtA AONS的合成潜力，其被应用于合成一系列新型α-氨基酮。
