Modulation of mycelial formation in Streptomyces toxytricini and enhancement of lipstatin using light

Scanty reports exist on Streptomyces toxytricini, a natural producer of the anti-obesity pro-drug lipstatin. For the first time, a study has been conducted on the regulation of its secondary metabolite synthesis using light. The present study investigates the impact of multiple light conditions on mycelial hyphal development and lipstatin production in S. toxytricini. Upon examining the mycelial, hyphal, and pellet morphogenesis under various light conditions, the differential pattern from dense pellet to loose mycelial hyphae was observed in the submerged fermentation condition. Biomass accumulation, as indicated by dry cell weight (DCW), showed a significant increase under red (4.2 g/L), indigo (4 g/L), green (4.13 g/L), yellow (3.37 g/L), and violet light (3.53 g/L) conditions. The maximum biomass was observed under red light, showing a four-fold increase compared with the dark condition (1 g/L). Along with the biomass and mycelial arrangements, red light produced significantly smaller pellet sizes (81.4 ± 13 μm) than the dark (784.7 ± 46 μm) and white-light (332.5 ± 59 μm) conditions. The HPLC analysis confirmed the significant effect of the red-light condition on lipstatin yield, with ~ 6 g/L, five-fold higher than ~ 1.2 g/L in white light and 300-fold higher than ~ 0.02 g/L in dark conditions. Besides that, in silico analysis of the photoreceptors identified two putative bacteriophytochrome (BphP) containing proteins in S. toxytricini, suggesting a potential sensory framework of red-light perception. Collectively, this work highlights light as a promising and easily implementable process parameter for enhancing secondary metabolite production, providing a foundation for future mechanistic and omics-based investigations.