Heterologous expression of a biosynthesis gene cluster from Amycolatopsis sp. resulted in the discovery of two unique class IV lasso peptides, felipeptins A1 and A2. A mixture of felipeptins stimulated proliferation of cancer cells, while having no such effect on the normal cells. Detailed investigation revealed, that pre-treatment of cancer cells with a mixture of felipeptins resulted in downregulation of the tumor suppressor Rb, making the cancer cells to proliferate faster. Pre-treatment with felipeptins made cancer cells considerably more sensitive to the anticancer agent doxorubicin and re-sensitized doxorubicin-resistant cells to this drug. Structural characterization and binding experiments showed an interaction between felipeptins resulting in complex formation, which explains their synergistic effect. This discovery may open an alternative avenue in cancer treatment, helping to eliminate quiescent cells that often lead to cancer relapse.

从生物合成基因簇的异源表达拟无枝酸sp。导致发现了两种独特的IV类套索肽，felipeptins A1和A2。脂肽的混合物刺激癌细胞的增殖，而对正常细胞没有这种作用。详细研究表明，用脂肽素混合物对癌细胞进行预处理会导致抑癌基因Rb的下调，从而使癌细胞增殖更快。用脂肽素进行的预处理使癌细胞对抗癌药阿霉素的敏感性大大提高，并使对阿霉素耐药的细胞再次对该药物敏感。结构表征和结合实验表明，脂肽之间的相互作用导致复合物的形成，这解释了它们的协同作用。这一发现可能为癌症治疗开辟一条替代途径，