Nocathioamides, Uncovered by a Tunable Metabologenomic Approach, Define a Novel Class of Chimeric Lanthipeptides

Abstract

The increasing number of available genomes,i n combination with advanced genome mining techniques,u nveiled ap lethora of biosynthetic gene clusters (BGCs) coding for ribosomally synthesized and post-translationally modified peptides (RiPPs). The products of these BGCs often represent an enormous resource for new and bioactive compounds,b ut frequently,they cannot be readily isolated and remain cryptic. Here,w ed escribe at unable metabologenomic approach that recruits asynergism of bioinformatics in tandem with isotopeand NMR-guided platform to identify the product of an orphan RiPP gene cluster in the genomes of Nocardia terpenica IFM 0406 and 0706 T .T he application of this tactic resulted in the discovery of nocathioamides family as afounder of anew class of chimeric lanthipeptides I.

Stable Isotope-Guided Metabolomics Reveals Polar-Functionalized Fatty-Acylated RiPPs from Streptomyces

“…14,15 Such changes in the chemical shift have been reported in related compounds, including albopeptin B 5 and nocathioamides. 15 The NMR spectra of solabiomycin B were almost identical to those of solabiomycin A, except that the series of signals corresponding to Ile4 was replaced by a series of signals corresponding to Val. Thus, solabiomycin B is very likely an analogue of solabiomycin A in which the Ile residue is substituted with a Val residue, which is consistent with the amino acid analysis and the differences in the sequences of plausible precursor peptides.…”

Substrate Recognition by the Peptidyl-(S)-2-mercaptoglycine Synthase TglHI during 3-Thiaglutamate Biosynthesis

“… 1 In contrast, preliminary activity experiments with TglHI indicated partial activity toward a 41mer TglACys C-terminal fragment lacking residues 1–10 and no activity toward further N-terminally truncated 31mer and 21mer fragments. 1 Considered together, these results suggest that the RREs of TglB and TglI might have evolved to recognize entirely different regions of the TglA precursor peptide—a natural “hybrid” of two different RiPP posttranslational modification systems similar to other examples that are found naturally 23 − 28 and to the artificial RiPP hybrids constructed recently in several laboratories. 29 − 34 However, from a practical perspective, a 41mer or 51mer TglACys substrate would complicate detailed structural and mechanistic investigations of the highly unusual TglHI reaction.…”

Two Bioactive Compounds, Uniformides A and B, Isolated from a Culture of Nocardia uniformis IFM0856T in the Presence of Animal Cells

“…The genus Nocardia , which is a rare actinomycete, consists of approximately 120 species; some are known to exist in water and soil, while thers are found in the human skin, lungs, and other organs as pathogens. The pathogenic genus Nocardia produces structurally complex and bioactive compounds, such as nocathioamides isolated from Nocardia terpenica , and nocardithiocin isolated from Nocardia pseudobrasiliensis . In our previous reports, we suggested a method of investigating a new natural compound by culturing the genus Nocardia in the presence of animal cells, to isolate new compounds , and known compounds that were not produced in a single culture of the genus Nocardia .…”