pubs.acs.org
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 IC50 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.