3ZDN

D11-C mutant of monoamine oxidase from Aspergillus niger

3ZDN の概要

• エントリーDOI: 10.2210/pdb3zdn/pdb
• 分子名称: MONOAMINE OXIDASE N, 1,2-ETHANEDIOL, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, flavin dependent oxidase, amines
• 由来する生物種: ASPERGILLUS NIGER
• 細胞内の位置: Peroxisome (Probable): P46882
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 224858.72

構造登録者

Frank, A.,Ghislieri, D.,Willies, S.,Turner, N.J.,Grogan, G. (登録日: 2012-11-29, 公開日: 2013-10-09, 最終更新日: 2023-12-20)

主引用文献

Ghislieri, D.,Green, A.P.,Pontini, M.,Willies, S.C.,Rowles, I.,Frank, A.,Grogan, G.,Turner, N.J.
Engineering an Enantioselective Amine Oxidase for the Synthesis of Pharmaceutical Building Blocks and Alkaloid Natural Products.
J.Am.Chem.Soc., 135:10863-, 2013

PubMed Abstract: The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine.

PubMed: 23808566
DOI: 10.1021/JA4051235

実験手法

X-RAY DIFFRACTION (2.55 Å)