A new NMR-based method to access to the unique components of the drug-like natural product metabolome of termite-gut associated actinomycetes has been developed. This approach was used to accelerate the identification of lead-like enhanced fractions containing small molecules with unique spectral patterns. The effectiveness of the approach was demonstrated by the isolation and identification of six new natural products, namely, actinoglycosidines A (1) and B (2), actinopolymorphol D (3), niveamycin A (7), B (8) and C (9).