Production and Characterization of Taxol as Anticancer Agent from Aspergillus terreus

Abstract

Taxol, a diterpenoid was initially isolated from the bark of Taxus brevifolia, approved by FDA in 1994 as a powerful drug for metastatic ovarian carcinoma, breast and lung cancer. However, due to limitations in the production of this drug based on this plant source, the productive potentiality of fungi of this compound opened a new avenue for its commercial production. In this study, among the twenty fungal isolates screened for Taxol production, Aspergillus terreus had the highest potentiality to produce Taxol (131.2 µg/ml). The productivity of Taxol by A. terreus has been maximized by nutritional optimization using inhibitors and growth regulators. The yield of Taxol by A. terreus was maximally obtained (0.663µg/ ml) by growing the fungal isolate on potato dextrose broth medium, amended with addition of biotin at 150 µg/ml for 20 days. The chemical structure Taxol extracted of A. terreus has been verified by proton and carbon NMR, IR and UV analyses. The activity of A. terreus Taxol has been assessed towards multiple cell lines, displaying a strong anticancer activity. In conclusion, the productivity of Taxol by A. terreus has been greatly improved upon using biotin as chemical modulator, that open a new avenue for commercializing the Taxol yield by fungi.

Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation

“…So many natural compounds are reported to use as antibiotics, anticancer agents. Many endophytic fungi isolated from different medicinal plants are reported to be main source of many secondary metabolites and pharmaceutical compounds with biotechnological roles [ 3 , 11 , 12 , 13 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 32 , 34 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 78 , 79 , 97 , 99 , 100 , 101 , 102 , 103 , 104 ]. Fusarubin and anhydrofusarubin, isolated from the Cladosporium species an endophyte of Rauwolfia serpentina , displayed a promising antimicrobial and antitumor activities [ 105 ].…”

“…and Phomopsis from the same host plant “Taxus” [ 128 ]. Notably, all the endophytes producing taxol are naturally resistant to taxol which has been shown as a powerful fungicide to plethora of phytopathogenic fungi [ 25 , 28 , 34 , 54 , 57 , 64 , 99 , 103 ]. Taxomyces andreanae was the first isolated Taxol-producing endophyte from Taxus spp., raising the hope for production of taxol via fermentation process, because of its fast growth on simple cultural media, possibility for growing on bulk fermenters, resistance to shearing and feasibility for genetic manipulation [ 18 ].…”

“…Mevalonic acid is synthesized from acetyl-CoA derived from nutrients (Figure 2 2). In this pathway, pyruvic acid was complexed with glyceraldehyde 3-phosphate by deoxyxylulose phosphate synthase forming deoxyxylulose 5-phosphate (DXP) which undergoes reduction forming methylerythritol 4-phosphate (MEP) which undergoes multiple steps forming Isopentenyl pyrophosphate (IPP) and its isomer dimethyallyl pyrophosphate (DMAPP) [13,[21][22][23][24][25]32,34,[54][55][56][57][58][59][60][61][62][63][64].…”

“…The steps of Taxol biosynthesis started with (1) coupling of isopentenyl pyrophosphate with farnesyl pyrophosphate via geranylgeranyl pyrophosphate synthase (GGPPS) forming Methylerythritol 4-phosphate (MEP) or non-mevalonate pathway (NMVA) or Deoxy-xylulose phosphate (DXP pathway) synthesizes isopentenyl pyrophosphate and dimethylallyl pyrophosphate in plastid of plant cell, independent on mevalonic acid (Figure 2). In this pathway, pyruvic acid was complexed with glyceraldehyde 3-phosphate by deoxyxylulose phosphate synthase forming deoxyxylulose 5-phosphate (DXP) which undergoes reduction forming methylerythritol 4-phosphate (MEP) which undergoes multiple steps forming Isopentenyl pyrophosphate (IPP) and its isomer dimethyallyl pyrophosphate (DMAPP) [13,[21][22][23][24][25]32,34,[54][55][56][57][58][59][60][61][62][63][64].…”

“…Precursor feeding is a strategy of exogenously presenting a biosynthetic precursor or different intermediates in the biosynthetic pathway to the culture medium to enhance the desired product yield [3,[11][12][13][21][22][23][24][25][26][27][28][32][33][34][54][55][56][57][58][59]64,78,79,97,[99][100][101][102][103][104]. It is a broadly used approach in plant cell/ tissue cultivation and being explored in the fermentation of endophytic fungi.…”