Fig. 4: In silico prediction of lipodiscamide biosynthesis and biochemical study of discodermin biosynthesis.

a, Putative lipodiscamide BGC. Shown above the NRPS and PKS proteins are the predicted substrate specificities for the respective A and AT domains. The module architectures and predicted substrate specificities fit well to the chemical structure of lipodiscamide A. As an example, the KR-catalyzed reaction of α-ketoisovaleric acid to the corresponding α-hydroxyl moiety is shown. A full biosynthetic scheme is provided in Extended Data Fig. 2. b, BGC encoding the discodermin NRPS. Shown above the NRPS proteins are the predicted substrate specificities for the respective A domains. A full biosynthetic scheme is provided in Extended Data Fig. 3. The reaction of the rSAM methyltransferase DscE acting on discodermin intermediates is shown. c, HPLC–HRMS traces of in vitro reconstitutions with native (pacman shape) or heat-denatured DscE (noodle shape) and discodermin D or discodermin B (wedges). Depicted are extracted ion chromatograms (EICs). Total ion counts of HPLC–HRMS runs are provided in Supplementary Fig. 21. d, HPLC–HRMS traces of isolated discodermin A (blue), B (purple) and D (orange) serving as analytical standards for reactions shown in c (color-coded similarly). HPLC–HRMS traces on all further control reactions are provided in Supplementary Fig. 23. Kiv, α-ketoisovaleric acid; CAL, CoA-acyl ligase; Fmt, formyltransferase.