Biotransformation optimization of betulin into betulinic acid production catalysed by cultured Armillaria luteo-virens Sacc ZJUQH100-6 cells.

Aims: Betulinic acid has attracted attention in terms of its important biological and pharmacological characteristics. The main objective of this work was to optimize the variables of biotransformation process in order to enhance betulinic acid production from betulin catalysed by fungus Armillaria luteo-virens Sacc ZJUQH100-6. Methods and Results: Fractional factorial design and response surface methodology were applied to optimize the main parameters that affect betulinic acid production in the growing-cells system. Results indicated that the addition of Tween 80 and substrate concentration were identified as the significant factors on betulinic acid formation, and the central composite experimental design was then adopted to derive a statistical model for optimizing biotransformation conditions. The optimum conditions were observed at pH 6 center dot 0, 0 center dot 57% Tween 80, 15 mg l-1 betulin and at 3 days of stage of inoculation. Conclusions: Under the optimized conditions, the highest productivity of betulinic acid predicted was 9 center dot 32%, which increased by 74 center dot 53% in comparison with that of the nonoptimized. The verified experiment revealed that the model can well simulate betulin biotransformation. Moreover, the bioconversion of betulin and betulin-28-monooxygenase activities was compared between the optimized and the nonoptimized conditions. Significance and Impact of the Study: Current data imply that betulinic acid production from betulin can be effectively enhanced through biotransformation optimization strategy.