Motivated by the mutation theory of quivers with potentials developed by Derksen-Weyman-Zelevinsky, and the representation-theoretic approach to cluster algebras it provides, we propose a mutation theory of species with potentials for species that arise from skew-symmetrizable matrices that admit a skew-symmetrizer with pairwise coprime diagonal entries. The class of skew-symmetrizable matrices covered by the mutation theory proposed here contains a class of matrices that do not admit global unfoldings, that is, unfoldings compatible with all possible sequences of mutations.