Activity and Biocatalytic Potential of an Indolylamide Generating Thioesterase

IF 4.9 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2024-10-21 DOI:10.1021/acs.orglett.4c03648

Weimao Zhong, Zachary L. Budimir, Lucas O. Johnson, Elizabeth I. Parkinson, Vinayak Agarwal

引用次数: 0

Abstract

The chemical synthesis of N-acyl indoles is hindered by the poor nucleophilicity of indolic nitrogen, necessitating the use of strongly basic reaction conditions that encumber elaboration of highly functionalized scaffolds. Herein, we describe the total chemoenzymatic synthesis of the bulbiferamide natural products by the biochemical activity reconstitution of a nonribosomal peptide synthetase assembly line-derived (NRPS-derived) thioesterase that neatly installs the macrocyclizing indolylamide. The enzyme represents a starting point for biocatalytic access to macrocyclic indolylamide peptides and natural products.

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吲哚酰胺生成硫酯酶的活性和生物催化潜力

由于吲哚氮的亲核性较差，N-酰基吲哚的化学合成受到阻碍，因此必须使用强碱性反应条件，从而限制了高功能化支架的制备。在本文中，我们描述了一种非核糖体肽合成酶组装线衍生（NRPS-derived）硫酯酶的生化活性重组，该酶能整齐地安装大环化吲哚酰胺，从而以化学酶法完全合成了bulbiferamide天然产物。这种酶是生物催化获取大环吲哚酰胺肽和天然产物的起点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.