Phylogenomic Identification of a Highly Conserved Copper-Binding RiPP Biosynthetic Gene Cluster in Marine Microbulbifer Bacteria

Conserved biosynthetic
gene clusters (BGCs) are often tied to the
production of natural products that perform critical functions in
an organism’s physiology and ecological interactions. Here,
by phylogenetic analysis across the bacterial genus, we report the
obligate conservation of a BGC in genomes of cosmopolitan marine Microbulbifer bacteria. This genus is a common member
of marine microbiomes, and this BGC was conserved in Microbulbifer genomes regardless of phylogenetic
or geographical dispersal. The post-translationally modified peptidic
product encoded by this BGCwhich was accessed via heterologous
production and its structure elucidated using a combination of mass
spectrometry and NMR spectroscopywas found to be a copper
chelator. Similar BGCs were then found in genomes of other marine
bacterial genera coinhabiting the microbiomes of sponges and corals.
The phylogenomic workflows described herein were implemented in a
pedagogic setting at the Georgia Institute of Technology to provide
hands-on instruction to undergraduate students in bacterial phylogeny,
genome mining, and natural product chemistry.