Metabologenomics-Driven\nDiscovery of Nocardimicins\nfrom a Psychrophilic <i>Nocardia</i> sp. Strain

A combined strategy of 2D-NMR-metabolomics-driven substructure\ntracking with genome mining led to the targeted discovery of 10 nocobactin-type\nlipopeptides (<b>1</b>–<b>10</b>) from the Arctic-derived\nphychrophillic <i>Nocardia</i> sp. L-016, among which <b>1</b>–<b>5</b> are new compounds, named nocardimicins\nS–W. The phenoxazole moiety in <b>1</b>–<b>10</b>, featuring unique NMR values and correlations, was used\nas a probe for tracking nocardimicin analogues. The structures of <b>1</b>–<b>5</b> were established based on extensive\nMS and NMR spectroscopic analyses. The biosynthesis of nocardimicins\n(<b>1</b>–<b>10</b>) in <i>Nocardia</i> sp. L-016 is proposed to be achieved by the <i>noc</i> biosynthetic gene cluster, which is composed of two sub-gene clusters\n(I and II) separated by a 228 kb region. Compounds <b>1</b>–<b>10</b> showed moderate inhibition against human cancer cell lines\nof HCT116 and HepG2 with IC<sub>50</sub> values in the range of 3.5–10.2\nμM. This work provides an effective application of paired-omics\ntechnologies in the discovery of new natural products.