Metabologenomics-Driven Discovery of Nocardimicins from a Psychrophilic Nocardia sp. 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 Nocardia sp. L-016, among which 1 – 5 are 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 – 5 were established based on extensive MS and NMR spectroscopic analyses. The biosynthesis of nocardimicins ( 1 – 10 ) in Nocardia sp. L-016 is proposed to be achieved by the noc biosynthetic gene cluster, which is composed of two sub-gene clusters (I and II) separated by a 228 kb region. Compounds 1 – 10 showed moderate inhibition against human cancer cell lines of HCT116 and HepG2 with IC 50 values 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.