Production of Mycophenolic Acid by Penicillium brevicompactum Using Solid State Fermentation

Abstract

Solid-state fermentation using the microfungus Penicillium brevicompactum for the production of mycophenolic acid is reported in this paper. Of the initial substrates tested (whole wheat, cracked wheat, long grain Basmati rice, and short grain Parmal rice), Parmal rice proved to be the best. Under initial conditions, using steamed Parmal rice with 80% (w/w) initial moisture content, a maximum mycophenolic acid concentration of 3.4 g/kg substrate was achieved in 12 days of fermentation at 25 °C. The above substrate was supplemented with the following additional nutrients (g/L packed substrate): glucose 40.0, peptone 54.0, KHPO 8.0, MgSO4⋅7HO 2.0, glycine 7.0, and methionine 1.65 (initial pH 5.0). A small amount of a specified trace element solution was also added. The final mycophenolic acid concentration was increased to nearly 4 g/kg substrate by replacing glucose with molasses. Replacing Parmal rice with rice bran as substrate further improved the mycophenolic acid production to nearly 4.5 g/kg substrate.

The Application of Solid State Fermentation for Obtaining Substances Useful in Healthcare

“…It has been demonstrated that in some cases the yield of microbial metabolites significantly increased when the strain was subjected to gamma ray -it increased the quantity of obtained mycophenolic acid produced by two strains of Penicillium requeforti [43] in comparison of other cited studies which involved unmodified Penicillium brevicompactum [39,41]. On the other hand, UV radiation was used for the modification of Tolypocladium inflatum which was used for the production of Cyclosporin A [47], however, in the case of that substance there were other studies which resulted in much higher yields [44,45].…”

“…However, in the majority of cases authors added some nutrients to agricultural waste to provide better results of releasing bioactive compounds. In the case of mycophenolic acid produced P. brevicompactum MTCC 8010 from rice bran those supplements were: peptone, KH 2 PO 4 , glycine and methionine [41]. On the other hand, in the case of P. brevicompactum ATCC 16024, the addition of mannitol or (NH 4 ) 2 HPO 4 to pearl barley did not enhance the MA synthesis [39].…”

“…Based on cited papers it might be stated that Penicillium brevicopactum is most common in the research regarding production of mycophenolic acid in SSF [38][39][40][41][42][43]. Those fungi produce polyketide synthase encoded by mpaC gene along with other enzymes such us: protein transacylase, β-ketoacylsynthase, acyltransferase, acyl carrier protein, and methyltransferase (MT) domains [106].…”

Antibiotic-free expression system for the production of human interferon-beta protein

“…High cell density cultivation of recombinant E. coli cells expressing rhIFN-β protein was done in a laboratory scale bioreactor. The fermentation was carried out in a 3.5 L reactor (Bioflow 3000, NBS with 2-2.5 L working volume) at 37 °C, as described previously (Patel et al 2016;Patil et al 2016). Briefly, in a typical experiment, glycerol stock of recombinant E. coli cells was streaked on a Luria-Bertani (LB)-agar plates containing 50 μg/ml carbenicillin and incubated at 37 °C for ~ 16 h. A single colony of the bacterial cells from the plate was inoculated in 10 ml LB medium, containing 50 μg/ml carbenicillin and incubated overnight at 37 °C (200 rpm).…”

Liposomal Delivery of Mycophenolic Acid With Quercetin for Improved Breast Cancer Therapy in SD Rats

“…Mycophenolic acid (MPA) is a secondary metabolite which is mainly produced by fungal species specialy Penicillium brevicompactum (Engel et al, 1982;Schneweis et al, 2000;Puel et al, 2005;Xu and Yang, 2007;Patel et al, 2016Patel et al, , 2017. It has diverse biological properties generally used for the treatment of rejection after organ transplant, psoriasis, and other autoimmune disorders; apart from this MPA also reported as a anticancer agent (Eugui et al, 1991;Zolezzi, 2005;Zheng et al, 2011).…”