Synthetic biology defies traditional views about the scope of biological inquiry (Hull 1978; Waters 2007; Weber 2013). Some authors are skeptical about the epistemic value the field has to the rest of the life sciences (Keller 2009a). This paper demonstrates how artificial biochemistries of life serve an essential epistemic function as semifactual models in biology (Knuuttila and Koskinen 2021). As semifactual models, alternative biochemistries of life facilitate the testing of hypotheses about universal biological constraints. Importantly, clarifying this role also unveils further research questions that would lend greater rigor to synthetic biology research programs.