New lipodepsipeptides, octaminomycins C and D (1 and 2), were discovered in an engineered Streptomyces sp. strain overexpressing the LysR transcriptional regulator family. The structures of 1 and 2 were elucidated by comprehensive analysis of their UV, HRMS, and NMR data. The absolute configurations were determined using spectroscopic analysis, the advanced Marfey's method, and genomic analysis. Genomic analysis enabled the identification of the nonribosomal peptide synthetase (NRPS) biosynthetic pathway of the octaminomycins.