Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, UK.
College of Science and Arts in Gurayat, Jouf University, King Khaled Road, Aljouf 42421, Saudi Arabia.
Molecules. 2023 Jan 1;28(1):354. doi: 10.3390/molecules28010354.
Indole-containing acyloins are either key intermediates of many antimicrobial/antiviral natural products or building blocks in the synthesis of biologically active molecules. As such, access to structurally diverse indole-containing acyloins has attracted considerable attention. In this report, we present a pilot study of using biotransformation to provide acyloins that contain various indole substituents. The biotransformation system contains the tryptophan synthase standalone β-subunit variant, TrpB, generated from directed evolution in the literature; a commercially available L-amino acid oxidase (LAAO); and the thiamine-diphosphate (ThDP)-dependent enzyme NzsH, encoded in the biosynthetic gene cluster () of the bacterial carbazole alkaloid natural product named neocarazostatin A. The utilization of the first two enzymes, the TrpB variant and LAAO, is designed to provide structurally diverse indole 3-pyruvate derivatives as donor substrates for NzsH-catalysed biotransformation to provide acyloin derivatives. Our results demonstrate that NzsH displays a considerable substrate profile toward donor substrates for production of acyloins with different indole ring systems, suggesting that NzsH could be further explored as a potential biocatalyst via directed evolution to improve the catalytic efficiency in the future.
含吲哚的酰基醇既是许多抗菌/抗病毒天然产物的关键中间体，也是生物活性分子合成中的构建模块。因此，获得结构多样的含吲哚的酰基醇引起了相当大的关注。在本报告中，我们介绍了使用生物转化来提供含有各种吲哚取代基的酰基醇的初步研究。生物转化系统包含来自文献中定向进化的色氨酸合酶独立β亚基变体 TrpB；一种市售的 L-氨基酸氧化酶（LAAO）；以及依赖于硫胺素二磷酸（ThDP）的酶 NzsH，它编码在细菌咔唑生物碱天然产物 neocarazostatin A 的生物合成基因簇（）中。前两种酶，TrpB 变体和 LAAO 的利用，旨在提供结构多样的吲哚 3-丙酮酸衍生物作为供体底物，供 NzsH 催化的生物转化生成酰基醇衍生物。我们的结果表明，NzsH 对用于生成具有不同吲哚环系统的酰基醇的供体底物表现出相当大的底物谱，这表明 NzsH 可以通过定向进化进一步探索作为潜在的生物催化剂，以提高未来的催化效率。
