Implication of mutagenesis and precursor supplementation towards the enhancement of lipstatin (an antiobesity agent) biosynthesis through submerged fermentation using Streptomyces toxytricini
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Date
2018
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3 Biotech
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.
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Keywords
Obesity · Lipstatin · Orlistat · Streptomyces toxytricini · Mutagenesis · Precursor supplementation