Wang Zhaochao, Yu Juanjuan, Wang Chenjie, Hua Yi, Wang Hong, Chen Jianwei
College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Mar Drugs. 2025 Jun 23;23(7):261. doi: 10.3390/md23070261.
Over the past decade, microbial natural products research has witnessed a transformative "deep-mining era" driven by key technological advances such as high-throughput sequencing (e.g., PacBio HiFi), ultra-sensitive HRMS (resolution ≥ 100,000), and multi-omics synergy. These innovations have shifted discovery from serendipitous isolation to data-driven, targeted mining. These innovations have transitioned discovery from serendipitous isolation to data-driven targeted mining. Genome mining pipelines (e.g., antiSMASH 7.0 and DeepBGC) can now systematically discover hidden biosynthetic gene clusters (BGCs), especially in under-explored taxa. Metabolomics has achieved unprecedented accuracy, enabling researchers to target novel compounds in complex extracts. Integrated strategies-combining genomic prediction, metabolomics analysis, and experimental validation-constitute new paradigms of current "deep mining". This review provides a systematic overview of 185 novel microbial natural products discovered between 2018 and 2024, and dissects how these technological leaps have reshaped the discovery paradigm from traditional isolation to data-driven mining.
在过去十年中，微生物天然产物研究经历了一个变革性的“深度挖掘时代”，这一时代由高通量测序（如PacBio HiFi）、超灵敏高分辨率质谱（分辨率≥100,000）和多组学协同等关键技术进步推动。这些创新将发现方式从偶然分离转变为数据驱动的靶向挖掘。基因组挖掘流程（如antiSMASH 7.0和DeepBGC）现在能够系统地发现隐藏的生物合成基因簇（BGC），尤其是在研究较少的分类群中。代谢组学已达到前所未有的准确性，使研究人员能够在复杂提取物中靶向新型化合物。结合基因组预测、代谢组学分析和实验验证的综合策略构成了当前“深度挖掘”的新范式。本综述系统概述了2018年至2024年间发现的185种新型微生物天然产物，并剖析了这些技术飞跃如何重塑了从传统分离到数据驱动挖掘的发现范式。
