Biosynthesis of unique natural product scaffolds by Fe(II)/αKG-dependent oxygenases

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL Journal of Natural Medicines Pub Date : 2025-02-06 DOI:10.1007/s11418-025-01880-z

Takayoshi Awakawa

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Abstract

Fe(II)/αKG-dependent oxygenases are multifunctional oxidases responsible for the formation of unique natural product skeletons. Studies of these enzymes are important because the knowledge of their catalytic functions, enzyme structures, and reaction mechanisms can be used to create non-natural enzymes through mutation and synthesize non-natural compounds. In this review, I will introduce the research we have conducted on two fungal Fe(II)/αKG-dependent oxygenases, TlxI-J and TqaL. TlxI-J is the first Fe(II)/αKG-dependent oxygenase type enzyme heterodimer that catalyzes consecutive oxidation reactions, hydroxylation followed by retro-aldol or ketal formation, to form the complex skeletons of meroterpenoids. TqaL is the first naturally occurring aziridine synthase, and I will discuss the mechanism of its unique C–N bond formation in nonproteinogenic amino acid biosynthesis. This review will advance research on the discovery of new enzymes and the analysis of their functions by reviewing the structures and functions of these extraordinary Fe(II)/αKG-dependent oxygenases, and promote their use in the synthesis of new natural medicines.

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铁(II)/α kg依赖性加氧酶生物合成独特天然产物支架。

铁(II)/α kg依赖性加氧酶是一种多功能氧化酶，负责形成独特的天然产物骨架。对这些酶的研究很重要，因为了解它们的催化功能、酶的结构和反应机理可以通过突变产生非天然酶和合成非天然化合物。本文将介绍两种真菌Fe(II)/α kg依赖性加氧酶TlxI-J和TqaL的研究进展。TlxI-J是第一个Fe(II)/α kg依赖性加氧酶型酶异二聚体，催化连续氧化反应，羟基化，然后形成反醛醇或酮，形成复杂的美罗萜类化合物骨架。TqaL是第一个天然存在的氮化吡啶合成酶，我将讨论其独特的C-N键在非蛋白质氨基酸生物合成中的形成机制。本文将通过对这些特殊的Fe(II)/α kg依赖性加氧酶的结构和功能的综述，为新酶的发现和功能分析提供科学依据，并促进其在天然新药合成中的应用。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.