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Updated: Mar 10, 2026

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脂质捐赠者定基因组挖掘揭示了二氧化,这是一种具有1,3-二氧化功能化的多不和脂质尾巴的抗菌脂

Ying Chen^1,2, Yunsheng Chen², Hao Xiang^2,3

¹School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University Shenzhen China xueyb@mail.sysu.edu.cn.

Chemical science

|March 9, 2026

概括

这项研究引入了一种新的基因组挖掘策略,通过专注于脂尾来发现新的脂抗生素. 它导致了对抗耐药细菌具有强烈活性的二氧化烯的鉴定.

科学领域:

微生物学微生物学
合成生物学合成生物学
药用化学医学化学

背景情况:

非核糖体脂抗生素是重要的抗菌剂,它们的有效性通常与它们的脂尾结构有关.
目前这些化合物的基因组挖掘方法主要集中在上,忽视了脂质供体生物合成的关键作用.

研究的目的:

开发和实施一种脂质捐赠者定基因组挖掘战略,以发现新型脂抗生素.
识别和表征新的脂支架,具有独特的脂尾修饰和抗菌特性.

主要方法:

利用多不和脂肪酸合成酶 (PUFAS) 核心基因作为基因组,以识别长多不和酸供体.
过用于同局部非核糖体合成酶 (NRPS) 组装线,以划分PUFAS-NRPS生物合成基因集群.
培养 *Chitinimonas koreensis* 来分离和表征新型脂,然后进行 *体外* 酶分析.

主要成果:

发现了60个精心策划的PUFAS-NRPS基因集群,包括蛋白质细菌中的一个新的*dxp*家族.
从*Chitinimonas koreensis*中分离出的二氧化,其特点是长的多不和脂质尾巴,具有由pyruvyl衍生的1,3-二氧化基因图案.
证明了pyruvylation是一种组装后的修饰,并且基因图案对于强大的抗菌活性对抗抗甲基西林耐药*黄金葡萄球菌*至关重要.

结论:

脂质捐赠者定基因组挖掘方法有效地扩大了脂质的化学多样性.
二氧化代表了一类新的非核糖体脂,具有显著的抗菌潜力,特别是对抗性菌株.
这一策略补充了以为中心的方法,使得人们能够获得功能上不同的抗生素支架.

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