Type III polyketide synthases (PKSs) are simple homodimer ketosynthases that distribute across plants, fungi, and bacteria, catalyzing formation of pyrone- and resorcinol-types aromatic polyketides with various bioactivities. The broad substrate promiscuity displayed by type III PKSs makes them wonderful candidates for expanding chemical diversity of polyketides. Violapyrone B (VLP B, 10), an α-pyrone compound produced by deepsea-derived Streptomyces somaliensis SCSIO ZH66, is encoded by a type III PKS VioA. We overexpressed VioA in three different hosts, including Streptomyces coelicolor M1146, Streptomyces sanyensis FMA as well as the native producer S. somaliensis SCSIO ZH66, leading to accumulation of different violapyrone compounds. Among them, S. coelicolor M1146 served as the host producing the most abundant violapyrones, from which five new (2-4, 7 and 12) and nine known (1, 5, 6, 8-11, 13 and 14) compounds were identified. Anti-influenza A (H1N1) virus activity of these compounds was then evaluated using ribavirin as a positive control (IC Biological background of the expression hosts is an important factor impacting on the encoding products of type III PKSs. By using S. coelicolor M1146 as cell factory, we were able to generate fourteen VLPs compounds. Anti-H1N1 activity assay suggested that the lipophilic nature of the alkyl chains of VLPs plays an important role for the activity, providing valuable guidance for further structural optimization of VLPs.