Exploring microbial natural products through NMR-based metabolomics.

Covering: 2000. 01 to 2025. 03The soaring demand for novel drugs has led to an increase in the requirement for smart methods to aid in the exploration of microbial natural products (NPs). Cutting-edge metabolomics excels at prompt identification of compounds from complex mixtures and accordingly accelerates the targeted discovery process. Although MS-based metabolomics has become a staple in this field, the utilization of NMR-based metabolomics has severely trailed in comparison. Herein, we summarize the key methodological advancements in 1D and 2D NMR techniques in the past two decades, especially for the invention of computational technologies and/or introduction of artificial intelligence for automated data processing, which significantly strengthen the ability of NMR-based metabolomics to analyze crude microbial extracts. Preliminary fractionation is advocated to deconvolute samples and thus enhance detection sensitivity towards minor components overshadowed by a complex matrix. Particularly, the synergistic application of NMR-based metabolomics and genomics provides an expedient approach to correlate biosynthetic gene clusters with cognate metabolites, greatly improving the efficiency of dereplication and, thus, targeted discovery of novel compounds. A variety of microbial NPs involving distinct chemical skeletons and/or biosynthetic logics are enumerated to prove the genuine prowess of NMR-based metabolomics. Overall, this review aims to encourage the broader adoption of NMR-based metabolomics in the realm of microbial NP research.