Genome mining, isolation, chemical synthesis and biological evaluation of a novel lanthipeptide, tikitericin, from the extremophilic microorganism Thermogemmatispora strain T81

Abstract

Tikitericin, a novel lanthipeptide was isolated and characterised together with its first total synthesis.

Genome Features and Secondary Metabolites Biosynthetic Potential of the Class Ktedonobacteria

“…Given that Gram-negative bacterial strains are becoming increasingly antibiotic resistant owing to their protective outer membranes and constitutively active efflux pumps, these mesophilic Ktedonobacteria strains may contribute to the development of novel antibiotics targeting Gram-negative bacteria (Miller, 2016; Domalaon et al, 2018). In turn, the antibacterial activities against S. aureus NBRC 13276, S. aureus NTCT8325, and S. aureus Mu50 might be explained by the production of novel lanthipeptides or other antimicrobial peptides by the Ktedonobacteria strains, as reported previously (Xu et al, 2018). Moreover, as the candidate testing microorganisms used for antimicrobial assays and activities assessed in the present study were finite and few isolated Ktedonobacteria species are available for study, this class likely harbors as-yet undisclosed bioactive functions.…”

“…It has been suggested that bacteria with complex morphological differentiation may possess an active secondary metabolism (Flärdh and Buttner, 2009; Manivasagan et al, 2014). Previously, metabolites of new acyloins and thiazoles have been identified in the fermentation broth of Thermosporothrix hazakensis SK20-1 T (Park et al, 2014, 2015), whereas the extremophilic Thermogemmatispora strain T81 produced a four (methyl) lanthionine-bridged new lanthipeptide that showed antimicrobial activity against the human pathogen Staphylococcus aureus (Xu et al, 2018). Furthermore, the released genome draft data revealed that the genome sizes of strain Thermogemmatispora onikobensis ONI-1 T (Komaki et al, 2016) and Thermogemmatispora carboxidivorans PM5 T were 5.56 and 5.61 Mb, respectively, whereas strain K. racemifer SOSP1-21 T supported a large genome of 13.66 Mb (Chang et al, 2011), which is the second largest bacterial genome identified to date following that of Sorangium cellulosum So0157-2 (14.78 Mb) (Han et al, 2013).…”

Dictyobacter vulcani sp. nov., belonging to the class Ktedonobacteria, isolated from soil of the Mt Zao volcano

“…The class Ktedonobacteria was initially established in 2006 for the Gram-positive, aerobic, mycelia-and spore-forming branching lineage in the phylum Chloroflexi [1] and, at the time or writing, contains six genera and 13 formally proposed mesophilic and thermophilic species [1][2][3][4][5][6][7][8][9]. Strains belonging to this class were characterized with actinomycete-like morphologies [1][2][3][4][5][6][7][8][9], relatively large genomes (5.54-13.66 Mb) [10][11][12], ubiquity in various terrestrial environments [13][14][15][16][17][18] and having potential for secondary metabolism [12,[19][20][21].…”

Ranking microbial metabolomic and genomic links in the NPLinker framework using complementary scoring functions

“…Linking microbial specialised metabolites to their producing BGCs has until recently mostly been done manually and on a small scale, working with single strains, either based on similarity to known, existing links (e.g. Xu et al (2018)), or predictions of unique identifying features of the spectrum from the BGCs (e.g. Kaweewan et al (2017)).…”

“…Duncan et al (2015)), establishing links between a BGC similar to a BGC with a known metabolite product, and a spectrum, can be considered particularly useful. This strategy, for example, was used to isolate the novel lanthipeptide tikitericin from a thermophilic bacterium (Xu et al, 2018). Lastly, since the expression of the metabolite is sometimes controlled by genes within the BGC, e.g.…”