PKS-NRPS hybrid synthetase; part of the gene cluster that mediates the fungal bioluminescence cycle (PubMed:30478037). Performs the biosynthesis of hispidin from caffeic acid by two cycles of addition of malonyl units followed by lactonization (PubMed:30478037). The fungal bioluminescence cycle begins with the hispidin synthetase that catalyzes the formation of hispidin which is further hydroxylated by the hispidin-3-hydroxylase, yielding the fungal luciferin 3-hydroxyhispidin. The luciferase then produces an endoperoxide as a high-energy intermediate with decomposition that yields oxyluciferin (also known as caffeoylpyruvate) and light emission. Oxyluciferin can be recycled to caffeic acid by caffeoylpyruvate hydrolase (PubMed:30478037) (Probable). (E)-caffeate + ATP + H(+) + 2 malonyl-CoA = AMP + 2 CO2 + 2 CoA + diphosphate + hispidin Secondary metabolite biosynthesis. The architecture of hips is the following one: adenylation (A), phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS) and malonyl-CoA:ACP transacylase (MAT). Hips homologs in bioluminescent species lack two domains, the ketoreductase (KR) and the dehydratase (DH) domains. The availability of a complete eukaryotic luciferin biosynthesis pathway provides several applications in biomedicine and bioengineering. In the N-terminal section; belongs to the NRP synthetase family.