Implication of mutagenesis and precursor supplementation towards the enhancement of lipstatin (an antiobesity agent) biosynthesis through submerged fermentation using Streptomyces toxytricini

Abstract

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.