In the present study, lipstatin production was studied from different mutants of Streptomyces toxytricini which were developed using ultraviolet radiation (exposure time 30 s, 1, 2, 5 and 10 min), ethyl methane sulfonte, methyl methane sulfonate (MMS) and N-methyl-N'-intro-N-nitrosoguanidine (NTG) treatments (50, 100, 200, 500, 1000 µM, respectively). Highest yielding mutants were provided precursor supplementation of citric acid, thiamine and biotin (each 1 g/L) at idiophase for further enhancement in the production of lipstatin. Screened mutants produced biomass in the range of 5.8-7.16 g/L which were lesser than control. Screened mutants also exhibited pellet morphology in submerged culture. Out of these mutants, NTG8 mutant produced highest amount of lipstatin (1383.25 mg/L) with 9.606 mg/L/h productivity. Precursor supplementation to this mutant further increased the production to 2387.81 mg/L. Mutant was validated in 5 L bioreactor and lipstatin production was enhanced to 2519.34 mg/L.
Keywords: Lipstatin; Mutagenesis; Obesity; Orlistat; Precursor supplementation; Streptomyces toxytricini.