An efficient process for the transformation of betulin to betulinic acid by a strain of Bacillus megaterium

Abstract

Betulinic acid as a derivative of betulin is widely reported for its anti-HIV and antitumor activities. Betulin has three most significant positions, i.e., primary hydroxyl group at position C-28, secondary hydroxyl group at position C-3, and alkene moiety at position C-20, where chemical modifications were performed to yield pharmacologically more active derivatives. Bioconversion optimization was performed for the enhancement in the percentage of conversion using statistical approach by opting temperature, pH and betulin concentration as independent variables. Three hundred fifty isolates were screened from natural sources under selective medium containing up to 3 g/l of betulin for their tolerance and bioconversion efficiency. Isolate KD235 was found to grow in 3 g/l betulin with 23.34 ± 0.57 g/l biomass and 0.67 ± 0.06 g/l betulinic acid production. New isolate KD235 was characterized by molecular analysis and named as Bacillus megaterium KD235. Molecular characterization of a potentially active isolate for the transformation of betulin to betulinic acid was suggested as isolate Bacillus megaterium KD235. Maximum bioconversion (22 ± 1.5%) was found at optimized conditions, i.e., pH 6.5, temperature 30°C and at 3 g/l betulin. Validations of experiments as *11% more bioconversion i.e., 1 ± 0.1 g/l betulinic acid were obtained using 5 l lab fermenter as compared to shake flask.

Biotransformation of food spice curcumin by gut bacterium Bacillus megaterium DCMB-002 and its pharmacological implications

“…The strain of B. megaterium has been found as an important bio-tool bacterium with wide application in food and medicine industry and agriculture [25][26][27][28][29][30]. It has exhibited biotransformation function by modifying natural products to obtain more active derives, such as converting betulin to betulinic acid with anti-HIV and antitumor activities, and bio-transforming ursolic acid to its derives with nitric oxide production inhibitory activity [26,29]. Herein seven compounds from them were identified by LC/(+)ESI-MS/MS analysis, among which transformation forms, inclusive of reduction of heptadione chain (adding 2 or 4 hydrogen atoms) and hydroxylation/demethylation/ demethoxylation of aromatic rings, were speculated.…”

A Review on Preparation of Betulinic Acid and Its Biological Activities

“…Rapid developments in metabolic engineering and synthetic biology provide alternative approaches for the increased production of natural products in microbial hosts [12][13][14][15]. The identification of newly identified microbes that convert betulin to BA is recently more intentioned [16], and metabolic engineering of key biosynthetic genes derived from plant sources has been reported as well. As a consequence, microbes that convert betulin to BA is recently more intentioned [16], and metabolic engineering of key biosynthetic genes derived from plant sources has been reported as well.…”

“…The identification of newly identified microbes that convert betulin to BA is recently more intentioned [16], and metabolic engineering of key biosynthetic genes derived from plant sources has been reported as well. As a consequence, microbes that convert betulin to BA is recently more intentioned [16], and metabolic engineering of key biosynthetic genes derived from plant sources has been reported as well. As a consequence, this review discusses recent developments in biotransformation and metabolic engineering for BA production.…”

Stimulatory Effects of Oleci Acid and Fungal Elicitor on Betulinic Acid Production by Submerged Cultivation of Medicinal Mushroom Inonotus obliquus

“…In previous studies, BA was mainly transformed from betulin by cultured resting cells [ 12 , 13 ]. In the present work, oleic acid and fungal elicitor from A. niger were proved to be effective inducers for BA accumulation in the submerged fermentation of I. obliquus .…”

“…Betulin is the precursor material of BA. In recent times, several reports have demonstrated that BA could be prepared through biotransformation process [ 11 , 12 , 13 ]. Meanwhile, betulin was used stimulatory agent to enhance mycelial biomass and production of exo-polysaccharides from I. obliquus [ 8 ].…”