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.

中文翻译：

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基因组采矿，分离，化学合成和新颖lanthipeptide的生物学评价，tikitericin，从嗜极微生物Thermogemmatispora菌株T81 †

新西兰极端嗜热微生物嗜热芽孢杆菌T81菌株的基因组挖掘表明存在生物合成机制，可产生几种不同的肽类天然产物。T81的固相培养导致了tikitericin 1的分离，tikitericin 1是一种新的瘦肽，其特征是具有四个（甲基）羊毛硫氨酸桥。tikitericin 1的质量导向分离和结构解析及其通过Fmoc-固相肽合成（SPPS）的全合成进行了描述。关键的非规范（甲基）羊毛硫氨酸残基在溶液相中通过改进的合成途径，随后使用Fmoc-SPPS组装以构建肽主链。还制备了替基替林的N末端截短类似物（2-5），以评估多环肽肽的每个顺序环对抗菌活性的贡献。