Metabologenomics-Driven Discovery of Nocardimicins from a Psychrophilic Nocardiasp. Strain

A combined strategy of 2D-NMR-metabolomics-driven substructure tracking with genome mining led to the targeted discovery of 10 nocobactin-type lipopeptides (1–10) from the Arctic-derived phychrophillic Nocardiasp. L-016, among which 1–5are new compounds, named nocardimicins S–W. The phenoxazole moiety in 1–10, featuring unique NMR values and correlations, was used as a probe for tracking nocardimicin analogues. The structures of 1–5were established based on extensive MS and NMR spectroscopic analyses. The biosynthesis of nocardimicins (1–10) in Nocardiasp. L-016 is proposed to be achieved by the nocbiosynthetic gene cluster, which is composed of two sub-gene clusters (I and II) separated by a 228 kb region. Compounds 1–10showed moderate inhibition against human cancer cell lines of HCT116 and HepG2 with IC50values in the range of 3.5–10.2 μM. This work provides an effective application of paired-omics technologies in the discovery of new natural products.