我科学家实现色氨酸“定制”卤化

Core Insights - A groundbreaking research achievement by a team from Hangzhou Normal University and Hubei University has been published in the Journal of the American Chemical Society, focusing on the rational design of a natural halogenase named AetF, which enables efficient synthesis of halogenated tryptophan [1][2] Group 1: Research Findings - The AetF enzyme, derived from cyanobacteria, is a single-component halogenase that combines halogenation and reduction functions, offering a more streamlined structure compared to traditional dual-component halogenases [2] - The natural AetF enzyme follows a fixed working pattern, halogenating tryptophan at the C5 position first, followed by the C7 position, which limits its flexibility for producing specific mono- or mixed-halogenated products [2] - The research team utilized high-resolution protein structures to design a mutant AetF-S523A, which significantly reduced halogenation activity at the C7 position, allowing for selective halogenation at the C5 position [3] Group 2: Methodology and Applications - The team further refined the substrate binding pocket by introducing larger residues, effectively blocking the C7 position and resulting in the AetF-AIF mutant, which exhibits nearly perfect specificity for C5 mono-halogenation [3] - A novel "one-pot" reaction strategy was developed, allowing for the efficient synthesis of two different mixed halogenated tryptophans (5-bromo-7-iodotryptophan and 5-iodo-7-bromotryptophan) with yields of 85% and 70%, respectively, without the need for toxic reagents or complex purification steps [3]