Zhang Wenhe, Ushimaru Richiro
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
School of Life Sciences and Biopharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road Shenhe, Shenyang 110016, China.
J Ind Microbiol Biotechnol. 2024 Dec 31;52. doi: 10.1093/jimb/kuaf024.
Cyanobacteria are prolific producers of structurally diverse and biologically potent natural products, a subset of which feature guanidino moieties. Introduction and modification of the guanidine group confer tuned basicity and enable extensive hydrogen bonding, cation-π, and electrostatic interactions, facilitating high-affinity binding to numerous biological targets. Although the enzymatic processes responsible for guanidine modifications in cyanobacterial pathways remain somewhat obscure, recent investigations have begun to clarify the biosynthetic machinery that mediates these distinctive transformations. In this review, we summarize these advances, with particular emphasis on the enzymatic steps responsible for guanidine installation and tailoring. These enzymatic transformations include N-prenylation, cyclization, and tricyclic guanidinium formation, representing rare or previously undescribed biosynthetic strategies in nature. This review provides new insights into the metabolic and enzymatic versatility of cyanobacteria and a foundation for future advances in enzyme engineering and therapeutic discovery. One-Sentence Summary: This review highlights recent advances in understanding how cyanobacteria enzymatically install and modify guanidino groups to produce bioactive natural products.
蓝细菌是结构多样且具有生物活性的天然产物的丰富生产者，其中一部分具有胍基部分。胍基的引入和修饰赋予了调节后的碱性，并能够实现广泛的氢键、阳离子-π和静电相互作用，促进与众多生物靶点的高亲和力结合。尽管负责蓝细菌途径中胍修饰的酶促过程仍有些模糊，但最近的研究已开始阐明介导这些独特转化的生物合成机制。在本综述中，我们总结了这些进展，特别强调了负责胍安装和修饰的酶促步骤。这些酶促转化包括N-异戊烯基化、环化和三环胍鎓形成，代表了自然界中罕见或以前未描述的生物合成策略。本综述为蓝细菌的代谢和酶促多功能性提供了新见解，并为酶工程和治疗发现的未来进展奠定了基础。一句话总结：本综述突出了在理解蓝细菌如何通过酶促方式安装和修饰胍基以产生生物活性天然产物方面的最新进展。
