Polyhydroxybutyrate (PHB) is a bacterial biopolymer with interesting features that make it useful in diverse areas of human development. The problem around this biomaterial is its high production cost, so researchers have focused their attention on the search of economic substrates to be used in the fermentation process. The present work is focused on designing a formulation based on mesquite honey and nejayote for cellular biomass and PHB generation by Bacillus cereus 4N, relying on the central compounds design and factorial design as statistical tools. The substrates employed were characterized by bromatological analysis and the biopolymer obtained from the fermentation process was analyzed by FT-IR. These results show that mesquite honey at 15 g/L influence a high cellular biomass