Phylogenetic and Chemical Diversity of a Hybrid-Isoprenoid-Producing Streptomycete Lineage

Abstract

Streptomyces species dedicate a large portion of their genomes to secondary metabolite biosynthesis. A diverse and largely marine-derived lineage within this genus has been designated MAR4 and identified as a prolific source of hybrid isoprenoid (HI) secondary metabolites. These terpenoid-containing compounds are common in nature but rarely observed as bacterial secondary metabolites. To assess the phylogenetic diversity of the MAR4 lineage, complementary culture-based and culture-independent techniques were applied to marine sediment samples collected off the Channel Islands, CA. The results, including those from an analysis of publically available sequence data and strains isolated as part of prior studies, placed 40 new strains in the MAR4 clade, of which 32 originated from marine sources. When combined with sequences cloned from environmental DNA, 28 MAR4 operational taxonomic units (0.01% genetic distance) were identified. Of these, 82% consisted exclusively of either cloned sequences or cultured strains, supporting the complementarity of these two approaches. Chemical analyses of diverse MAR4 strains revealed the production of five different HI structure classes. All 21 MAR4 strains tested produced at least one HI class, with most strains producing from two to four classes. The two major clades within the MAR4 lineage displayed distinct patterns in the structural classes and the number and amount of HIs produced, suggesting a relationship between taxonomy and secondary metabolite production. The production of HI secondary metabolites appears to be a phenotypic trait of the MAR4 lineage, which represents an emerging model with which to study the ecology and evolution of HI biosynthesis.

Marinocyanins, cytotoxic bromo-phenazinone meroterpenoids from a marine bacterium from the streptomycete clade MAR4

“…4 These observations are supported at the genomic level, with MAR4 strains averaging five ABBA prenyl-transferases per strain relative to less than one for other streptomycetes. 5 MAR4 hybrid isoprenoids encompass a diversity of structures including prenylated polyketides, phenazines, and pyrroles, and are of considerable interest due to their potent biological activities. 3–5 …”

“…5 MAR4 hybrid isoprenoids encompass a diversity of structures including prenylated polyketides, phenazines, and pyrroles, and are of considerable interest due to their potent biological activities. 3–5 …”

A new prenylated indole derivative from endophytic actinobacteria Streptomyces sp. neau-D50

“…Terpenoids are considered to be widespread in actinomycetes by genome mining analysis (Citron et al 2012); however, the hybrid isoprenoids are relatively uncommon in prokaryotes for reasons that are not understood (Kuzuyama & Seto 2003). Although less than 40 hybrid isoprenoids have been isolated from actinomycetes (Daum et al 2009;Heide 2009;Che et al 2012Che et al , 2013Kaysser et al 2012), the significant structural diversity and biological activity of these compounds render actinomycetes as important sources for hybrid isoprenoids-related drug discovery (Gallagher et al 2010(Gallagher et al , 2013. Furthermore, the isoprene moiety seems to be essential for the biological activities of the hybrid isoprenoids and may contribute to the diversity in the biological activities (Kumano et al 2008 Research, 2014Vol.…”

Intra‐clade metabolomic profiling of MAR4 Streptomyces from the Macaronesia Atlantic region reveals a source of anti‐biofilm metabolites

“…) (Prieto‐Davó et al ., ), while it is chemically closer to S. synnematoformans . Thus, our results support that the production of hybrid isoprenoids is a phenotypic trait that differentiates the two MAR4 clades (Gallagher et al ., ).…”

“…Previous studies have suggested a relationship between MAR4 phylogeny and hybrid isoprenoids production (Gallagher et al ., ) as well as to the number of gene clusters containing ABBA prenyltransferases (Gallagher and Jensen, ), which are the biosynthetic enzymes that have been reported to install isoprene units on target molecules and as such may regulate the bioactivity of molecules (Leipoldt et al ., ). Our results support the proposed relationships between evolutionary traits and secondary metabolite production which may be derived from homologous recombination of secondary metabolite genes resulting in highly specific metabolites for diverse niches (Jenke‐Kodama et al ., ), with the exception of strain PTM‐081, as stated above.…”