Biosynthesis of a bacterial meroterpenoid reveals a non-canonical class II terpene synthase

IF 7.6 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Chemical Science Pub Date : 2024-11-15 DOI:10.1039/d4sc06010e

Zengyuan Wang, Tyler Alsup, Xingming Pan, Lu-Lu Li, Jupeng Tian, Ziyi Yang, Xiaoxu Lin, Hui-Min Xu, Jeffrey D Rudolf, Liao-Bin Dong

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引用次数: 0

Abstract

Meroterpenoids are hybrid natural products that arise from the integration of terpenoid and non-terpenoid biosynthetic pathways. While the biosynthesis of fungal meroterpenoids typically follows a well-established sequence of prenylation, epoxidation, and cyclization, the pathways for bacterial perhydrophenanthrene meroterpenoids remain poorly understood. In this study, we report the construction of an engineered metabolic pathway in Streptomyces for the production of the bacterial meroterpenoid, atolypene A (1). Our research reveals a novel biosynthetic pathway wherein the structure of 1 is assembled through a distinct sequence of epoxidation, prenylation, and cyclization, divergent from its fungal counterparts. We demonstrate that the noncanonical class II terpene synthase (TS) AtoE initiates cyclization by protonating the epoxide via the E314 residue, which acts as a Brønsted acid within the characteristic E314TAE motif. Additionally, bioinformatic analysis of biosynthetic gene clusters (BGCs) that contain AtoE-like TSs supports that bacteria have the potential to produce a wide array of meroterpenoids.

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细菌 Meroterpenoid 的生物合成揭示了一种非典型 II 类萜合成酶

经萜类化合物是萜类和非萜类生物合成途径结合产生的混合天然产物。真菌类美拉德萜类化合物的生物合成通常遵循前炔化、环氧化和环化的既定顺序，而细菌类全氢菲美拉德萜类化合物的合成途径却鲜为人知。在本研究中，我们报告了在链霉菌中构建一条工程化代谢途径，用于生产细菌性 meroterpenoid，即 atolypene A (1)。我们的研究揭示了一种新的生物合成途径，在这种途径中，1 的结构是通过环氧化、前酰化和环化的独特序列组装而成的，与真菌中的同类结构不同。我们证明，非经典的第二类萜烯合成酶（TS）AtoE 通过 E314 残基质子化环氧化物来启动环化，E314 残基在特征 E314TAE 矩阵中充当布氏酸。此外，对含有类似 AtoE 的 TS 的生物合成基因簇 (BGC) 进行的生物信息学分析表明，细菌具有生产多种美拉泊类化合物的潜力。

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来源期刊

Chemical Science CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

14.40

自引率

4.80%

发文量

1352

审稿时长

2.1 months

期刊介绍： Chemical Science is a journal that encompasses various disciplines within the chemical sciences. Its scope includes publishing ground-breaking research with significant implications for its respective field, as well as appealing to a wider audience in related areas. To be considered for publication, articles must showcase innovative and original advances in their field of study and be presented in a manner that is understandable to scientists from diverse backgrounds. However, the journal generally does not publish highly specialized research.