Cystomanamides A-D were isolated as novel natural product scaffolds from Cystobacter fuscus MCy9118, and their structures were established by spectroscopic techniques including 2D NMR, LC-SPE-NMR/-MS, and HR-MS. The cystomanamides contain β-hydroxy amino acids along with 3-amino-9-methyldecanoic acid that is N-glycosylated in cystomanamide C and D. The gene cluster for cystomanamide biosynthesis was identified by gene disruption as PKS/NRPS hybrid incorporating an iso-fatty acid as starter unit and including a reductive amination step at the interface of the PKS and NRPS modules.