The Deep Mining Era: Genomic, Metabolomic, and Integrative Approaches to Microbial Natural Products from 2018 to 2024.

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.