Peptide display has enabled identification and optimization of ligands to many targets. These ligands are usually linear or disulfide-containing peptides that are vulnerable to proteolysis or reduction. We report yeast surface and phage display of lanthipeptides, macrocyclic ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain multiple thioether cross-links that bestow their biological activities. We developed C-terminal yeast display of the class II lanthipeptides lacticin 481 and haloduracin β, and randomization of the C-ring of the former was used to select tight binders to αvβ3 integrin. This represents the first examples of bacterial RiPP production in Saccharomyces cerevisiae for identification of variants with new biological activities. We also report N-terminal phage display of the class I lanthipeptide nisin and randomization of its A- and B-rings to enrich binders to a small molecule, lipid II. The successful display and randomization of both class I and II lanthipeptides demonstrates the versatility and potential of RiPP display.

中文翻译：

---

酵母和多种​​多肽多肽的噬菌体展示技术的开发和应用

肽展示已使鉴定和优化许多靶标的配体成为可能。这些配体通常是线性的或含二硫键的肽，它们易于蛋白水解或还原。我们报告了酵母表面和噬菌体展示的lanthipepteptes，大环核糖体合成和翻译后修饰的肽（RiPPs）。羊毛肽含有赋予其生物学活性的多个硫醚交联键。我们开发了II类lanthipeptides乳酸481和haloduracinβ的C端酵母显示，并使用前者C环的随机化来选择与αvβ3整联蛋白紧密的结合剂。这代表了酿酒酵母中细菌RiPP产生的第一个例子用于鉴定具有新生物活性的变体。我们还报告了I类lanthipeptide乳链菌肽的N末端噬菌体展示以及其A环和B环的随机化，以丰富小分子脂质II的结合剂。I类和II类瘦肽的成功展示和随机展示了RiPP展示的多功能性和潜力。