Organoselenium compounds are rare in nature but play important physiological roles by exploiting the distinct features of selenium. However, the ability to explore these compounds and their implications has been hindered by the limited availability of (bio)synthetic tools for the generation of organoselenium molecules, particularly the lack of enzymatic strategies for C‒Se bond formation. Here we develop an enzymatic approach for C‒Se bond formation using sulfur carrier proteins to biosynthesize the isologous selenium counterparts of cysteine, thiamine and a chuangxinmycin derivative. Our results indicate that widespread sulfur-carrier-protein-based biosynthetic systems provide promiscuous and programmable machinery for the production of unnatural Se-containing compounds. We anticipate that the ‘element engineering’ strategy used in this study will provide new opportunities to develop biologically rare molecules or abiological-element-containing chemicals not found in nature.

有机硒化合物在自然界中很罕见，但通过利用硒的独特特征发挥着重要的生理作用。然而，用于生成有机硒分子的（生物）合成工具的可用性有限，特别是缺乏用于 C-Se 键形成的酶促策略，阻碍了探索这些化合物及其影响的能力。在这里，我们开发了一种利用硫载体蛋白形成 C-Se 键的酶促方法，以生物合成半胱氨酸、硫胺素和创新霉素衍生物的同源硒对应物。我们的结果表明，广泛存在的基于硫载体蛋白的生物合成系统为非天然含硒化合物的生产提供了混杂且可编程的机器。我们预计，本研究中使用的“元素工程”策略将为开发自然界中未发现的生物稀有分子或含有非生物元素的化学物质提供新的机会。