Fig. 3: Metagenome-guided synthesis of bioactive small molecules.
From: Bioactive molecules unearthed by terabase-scale long-read sequencing of a soil metagenome
a, Left, general outline of targeted metagenomic NRPS assembly through HMM identification of A-domain-containing reads. Right, BiG-SCAPE analysis of 328 assemblies containing ≥4 A domains. Colored circles are metagenomic BGCs, with white circles denoting clusters matched from the MiBig database. b, Phylogeny breakdown of assemblies from a. c, Outline of the synBNP approach. d, Antibiotic activity screening of 55 synBNPs synthesized based on 20 metagenomic NRPS BGCs against B. subtilis (Bs), S. aureus (Sa) and E. coli (Ec). Lines separate predictions generated by single BGCs. e, Expanded activity screening of synBNPs with MICs ≤8 µg ml−1 from b against the ESKAPE pathogens and activity against HEK and HeLa human cell lines. Results in d,e are representative of two and three biologically independent replicates, respectively.
