The Unexplored Wealth of Microbial Secondary Metabolites: the Sphingobacteriaceae Case Study

Research on secondary metabolites (SMs) has been mostly focused on Gram-positive bacteria, especially Actinobacteria. The association of genomics with robust bioinformatics tools revealed the neglected potential of Gram-negative bacteria as promising sources of new SMs. The family Sphingobacteriaceae belongs to the phylum Bacteroidetes having representatives in practically all environments including humans, rhizosphere, soils, wastewaters, among others. Some genera of this family have demonstrated great potential as plant growth promoters, bioremediators and producers of some value-added compounds such as carotenoids and antimicrobials. However, to date, Sphingobacteriaceae's SMs are still poorly characterized, and likewise, little is known about their chemistry. This study revealed that Sphingobacteriaceae pangenome encodes a total of 446 biosynthetic gene clusters (BGCs), which are distributed across 85 strains, highlighting the great potential of this bacterial family to produce SMs. Pedobacter, Mucilaginibacter and Sphingobacterium were the genera with the highest number of BGCs, especially those encoding the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), terpenes, polyketides and nonribosomal peptides (NRPs). In Mucilaginibacter and Sphingobacterium genera, M. lappiensis ATCC BAA-1855, Mucilaginibacter sp. OK098 (both with 11 BGCs) and Sphingobacterium sp. 21 (6 BGCs) are the strains with the highest number of BGCs. Most of the BGCs found in these two genera did not have significant hits with the MIBiG database. These results strongly suggest that the bioactivities and environmental functions of these compounds, especially RiPPs, PKs and NRPs, are still unknown. Among RiPPs, two genera encoded the production of class I and class III lanthipeptides. The last are associated with LanKC proteins bearing uncommon lyase domains, whose dehydration mechanism deserves further investigation. This study translated genomics into functional information that unveils the enormous potential of environmental Gram-negative bacteria to produce metabolites with unknown chemistries, bioactivities and, more importantly, unknown ecological roles.