Mapping the BGCs to a species phylogeny from GTDB allowed us to see who's making (detectable) NRP metallophores. We found BGCs in 60% of Myxobacteria, 41% of Cyanobacteria, 35% of Actinobacteria, 18% of Proteobacteria, and just 3.3% of Firmicutes. Few were found outside these phyla.

Where can we find biosynthetic novelty? Cyanobacteria! We found them to be severely understudied. Nearly all BGCs were distinct from each other and from the two (!) known cyanobacterial NRP metallophores.

I applied the rules to 15k bacterial genomes to generate the first global census of NRP metallophore biosynthesis in bacteria (but certainly not the last!)

BiG-SCAPE networking showed that many BGCs are unlike anything found in MIBiG, and nearly 500 were only found in a single species! We also identified a couple of chelator combinations not found in any known BGCs

NRP metallophores have chelating substructures rarely found in other natural products, and genes encoding chelator biosyntheses are often in the BGC alongside the NRPS. I developed a series of HMMs to detect those chelator pathways.

Using this (not-so-)simple strategy, we could identify 78% of NRP metallophore BGCs with just a 3% false positive rate.

How do I know? Expert examination is still the best way to find metallophore BGCs, so I manually annotated 758 NRPS BGCs as a gold standard!