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Species of  Burkholderia  are highly versatile being found not only abundantly in soil, but also as plants and animals’ commensals or pathogens. Their complex multireplicon genomes harbour an impressive number of polyketide synthase (PKS) and nonribosomal peptide-synthetase (NRPS) genes coding for the production of antimicrobial secondary metabolites (SMs), which have been successfully deciphered by genome-guided tools. Moreover, genome metrics supported the split of this genus into  Burkholderia sensu stricto  (s.s.) and five new other genera. Here, we show that the successful antimicrobial SMs producers belong to  Burkholderia  s.s. Additionally, we reviewed the occurrence, bioactivities, modes of action, structural, and biosynthetic information of thirty-eight  Burkholderia  antimicrobial SMs shedding light on their diversity, complexity, and uniqueness as well as the importance of genome-guided strategies to facilitate their discovery. Several  Burkholderia  NRPS and PKS display unusual features, which are reflected in their structural diversity, important bioactivities, and varied modes of action. Up to now, it is possible to observe a general tendency of  Burkholderia  SMs being more active against fungi. Although the modes of action and biosynthetic gene clusters of many SMs remain unknown, we highlight the potential of  Burkholderia  SMs as alternatives to fight against new diseases and antibiotic resistance.

Burkholderia in the genomic era: from taxonomy to the discovery of new antimicrobial secondary metabolites