通过基于SPECO的基因组挖掘来探索核糖体合成和翻译后修改的
Gengfan Wu1, Longcheng Guo1, Beibei He1
1Department of Chemistry, The University of Hong Kong, Hong Kong, P.R. China.
Methods in enzymology
|July 12, 2025
概括
我们开发了一种新的基因组挖掘工作流,SPECO,以发现新的核糖体合成和翻译后修饰 (RiPPs). 这种方法克服了现有工具中的偏见,使得未经探索的细菌天然产品的探索成为可能.
科学领域:
- * 计算生物学和生物信息学.
- * 自然产品的发现.
- * 分子生物学和酶学.
背景情况:
- *基因组挖掘工具识别生物合成基因集群 (BGCs) 用于自然产品 (NP) 发现.
- * 由于对已知RiPP家族的偏见,现有的工具难以找到新型核糖体合成和翻译后修饰 (RiPPs).
- * 需要改进的方法来探索细菌中庞大的,未被探索的RiPP多样性.
研究的目的:
- * 开发一种新的基因组挖掘工作流程,SPECO (小和酶共发生),用于发现新的RiPP化学.
- * 提供一个整体的基因组挖掘方法,将SPECO与其他生物信息学工具 (如AlphaFold-Multimer) 整合在一起.
- *为了证明SPECO在发现尚未探索的RiPP生物合成中的实用性,以激进的S-adenosylmethionine (rSAM) 酶为例.
主要方法:
- * 开发了基于前体和修饰酶在细菌基因组中的共发生和共保存的SPECO分析工作流.
- *将SPECO与现有的生物信息工具集成为全面的基因组挖掘战略.
- * 应用了工作流来研究涉及基修饰的激进S-adenosylmethionine (rSAM) 酶.
主要成果:
- *SPECO工作流通过利用保存的生物合成逻辑有效地识别潜在的RiPP生物合成基因集群.
- *综合方法成功地揭示了尚未探索的酶功能,特别是与大环化相关的rSAM酶.
- * 展示了一种方法来克服当前基因组挖掘工具对RiPP发现的局限性.
结论:
- *SPECO工作流提供了一种强大的新策略,用于发现新型RiPP及其相关生物合成酶.
- *这种方法显著扩大了从细菌基因组中识别新天然产品的潜力.
- * 该方法在未来对细菌基因组序列的探索中非常适用,以发现新的RiPP生物合成和酶学.
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