Enzymatic synthesis of organoselenium compounds via C‒Se bond formation mediated by sulfur carrier proteins

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.