Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria

Abstract

A combination of small molecule chemistry, biosynthetic analysis, and genome mining has revealed the unexpected conservation of polycyclic tetramate macrolactam biosynthetic loci in diverse bacteria. Initially our chemical analysis of a Streptomyces strain associated with the southern pine beetle led to the discovery of frontalamides A and B, two previously undescribed members of this antibiotic family. Genome analyses and genetic manipulation of the producing organism led to the identification of the frontalamide biosynthetic gene cluster and several biosynthetic intermediates. The biosynthetic locus for the frontalamides’ mixed polyketide/amino acid structure encodes a hybrid polyketide synthase nonribosomal peptide synthetase (PKS-NRPS), which resembles iterative enzymes known in fungi. No such mixed iterative PKS-NRPS enzymes have been characterized in bacteria. Genome-mining efforts revealed strikingly conserved frontalamide-like biosynthetic clusters in the genomes of phylogenetically diverse bacteria ranging from proteobacteria to actinomycetes. Screens for environmental actinomycete isolates carrying frontalamide-like biosynthetic loci led to the isolation of a number of positive strains, the majority of which produced candidate frontalamide-like compounds under suitable growth conditions. These results establish the prevalence of frontalamide-like gene clusters in diverse bacterial types, with medicinally important Streptomyces species being particularly enriched.

Antifungal actinomycetes associated with the pine bark beetle, Orthotomicus erosus, in South Africa

“…Comparison of the eight strains included in this group revealed that they grouped within one of the three clades of Streptomyces spp. that were identified by Hulcr et al 30 This clade also included a strain isolated from the pine-infesting beetle D. frontalis 13,28 and cellulose degrading Streptomyces spp. associated with a pineinfesting siricid wasp, Sirex noctilio 30,31 .…”

“…The clade formed by our isolates and those from S. noctilio and D. frontalis was identified in another study. 32 Several previously reported isolates from pine-infesting insects 13,28,30,31 were grouped into two clades, based on their core genomes. One of these clades, containing a single isolate from both S. noctilio 31 and D. ponderosae had remarkable lignocellulose digestion capacity.…”

“…This clade was split between a branch consisting of a single isolate from D. frontalis (Streptomyces spp. SPB074) 13,28 and another clade that contained two branches, one with the eight isolates from this study and the other a clade with isolates from Sirex noctilio (Streptomyces sp. SA3ActG) 29 and D. frontalis (Streptomyces spp.…”

“…SA3ActG) 29 and D. frontalis (Streptomyces spp. SPB074) 28 . All of these branches were well supported.…”

Microbial Symbionts of Insects are the Focus of the First International Cooperative Biodiversity Group (ICBG) in Brazil

“…SPB78 isolated from same beetle ( Figure 5). 26 Similar symbiotic systems associated with social bees have scarcely been investigated yet. Pioneer studies in Brazil have recently reported that the Brazilian social stingless bee Scaptotrigona depilis cultivate a fungus to survive.…”