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

Chem Sci. 2018 Aug 20;9(37):7311-7317. doi: 10.1039/c8sc02170h. eCollection 2018 Oct 7.


Genome mining of the New Zealand extremophilic microorganism Thermogemmatispora strain T81 indicated the presence of biosynthetic machinery to produce several different peptidic natural products. Solid-phase culture of T81 led to the isolation of tikitericin 1, a new lanthipeptide characterised by four (methyl)lanthionine bridges. The mass-guided isolation and structural elucidation of tikitericin 1 is described together with its total synthesis via Fmoc-solid-phase peptide synthesis (SPPS). The key non-canonical (methyl)lanthionine residues were synthesised in solution phase via an improved synthetic route and subsequently assembled to construct the peptide backbone using Fmoc-SPPS. N-Terminal truncated analogues of tikitericin (2-5) were also prepared in order to evaluate the contribution of each sequential ring of the polycyclic lanthipeptide to the antibacterial activity.