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

Abstract

<jats:p>Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids “Taxol” is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree, Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark of T. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi from Taxus spp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceae and Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.</jats:p>

Customizing Functionalized Cofactor Mimics to Study the Human Pyridoxal 5′-Phosphate-Binding Proteome

“…After tryptic digest, peptides were analyzed using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) and compared with the PL -cultured control using label-free quantification (LFQ) (Figure 2B) (Cox et al., 2014). We detected 15 PLP -DEs (GO term 0030170: PLP binding; Ashburner et al., 2000) significantly enriched upon PL1 labeling in HEK293 compared with the control (Figure 2C and Table S1), which accounts for around 30% of the complete human pool of PLP -binding enzymes (53 reviewed proteins annotated with GO term 0030170: PLP binding within the human proteome [UniProt: 9606]; Ashburner et al., 2000), including members of fold types I, II, and IV (El-Sayed and Shindia, 2012). Several PLP -DEs related to cancer proliferation and tumor development (e.g., SHMT1; Renwick et al., 1998 or cytosolic aspartate aminotransferase, GOT1; Thornburg et al., 2008) or to Parkinson disease (Bras et al., 2008) and atherosclerosis (Park et al., 2008) (serine palmitoyltransferase 2, SPTLC2, and sphingosine-1-phosphate lyase 1, SGPL1) were identified.…”

“…PLP -DEs catalyze a diverse set of chemical reactions mainly with amino acid substrates, including decarboxylation, transamination, racemization, α , β , γ -substitution or α , β , γ -elimination (Percudani and Peracchi, 2003). Although sequence similarity is low among PLP -DEs, they are categorized into five distinct fold types guided by structural similarity (El-Sayed and Shindia, 2012). Due to the large number of chemical reactions catalyzed by PLP -DEs, they play a crucial role in cellular metabolism, ranging from amino acid biosynthesis and turnover to synthesis of neurotransmitters or tetrapyrroles (Parra et al., 2018).…”

Detection, Purification and Elucidation of Chemical Structure and Antiproliferative Activity of Taxol Produced by Penicillium chrysogenum

“…This CFS was extracted with double volume of dichloromethane (DCM). The organic extract was then evaporated using a rotary evaporator (IKA, RV10, Staufen im Breisgau, Germany) at 35 °C; the dried residue was resuspended in 3 mL methanol and analyzed using the necessary chromatographic and spectroscopic methods [ 21 , 47 ].…”

“…Total DNA was extracted from P. chrysogenum after its growth in potato dextrose broth (PDB) for 15 d [ 44 , 46 , 47 ]. The primers used for amplification of genes encoding 10-de-acetylbaccatin III-O-acetyltransferase (DBAT) that catalyze the immediate diterpenoid precursor of taxolwere5′-GGAGCCAATATGGAAGAGAGAAT-3′ as forward primer and 5′-TCCATG TTGCACGAGACTTAC-3′ as reverse primer (Promega Company, Madison, WI, USA) [ 43 ].…”

Effects of Bioflavonoids from Taxus Media var. Hicksii on Superoxide Generation, Phosphorylation of Proteins and Translocation of Cytosolic Compounds to the Cell Membrane in Human Neutrophils

“…Hicksii [1,2]. Most researchers have been devoted to studying on paclitaxel and its homologues from geuns Taxus owing to their outstanding anticancer effects [3].When it comes to bioflavonoids in Taxus, there's only a few research. However, several investigations have confirmed that biflavonoids has significant pharmacological activity, even though they are rare in nature and [4].…”