@article { ISI:000317939100003,
	title = {Biotransformation of vinblastine to vincristine by the endophytic fungus fusarium oxysporum isolated from catharanthus roseus},
	journal = {Biocatalysis and Biotransformation},
	volume = {31},
	number = {2},
	year = {2013},
	month = {APR},
	pages = {89-93},
	publisher = {INFORMA HEALTHCARE},
	address = {TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND},
	abstract = {<p>A fungal transformation method for the production of the less abundant but more valuable anticancer drug vincristine using the more abundant anticancer drug vinblastine by an endophytic fungus Fusarium oxysporum isolated from the plant Catharanthus roseus is described. Vinblastine dissolved in sterile water when incubated with the fungal mycelial mass was transformed into vincristine at room temperature. The biotransformation process was monitored by periodic sampling of aliquots that were extracted with ethyl acetate. The crude transformed compounds were analysed using TLC where the Rf value of the spot obtained on the 8th day was found to be similar to that of standard vincristine (Rf 0.74). Purification by HPLC using a C 18 symmetry column showed a peak with RT (34.9 min) similar to that of standard vincristine. Further characterization with the help of ESI-MS showed a peak at m/z 825 attributed to the (M + H)(+) ion. This indicated that the fungus Fusarium oxysporum had converted vinblastine to vincristine.</p>},
	keywords = {Biotransformation, endophytes, fusarium oxysporum, Vinblastine, vincristine},
	issn = {1024-2422},
	doi = {10.3109/10242422.2013.776544},
	author = {Kumar, Ashutosh and Ahmad, Absar}
}
@article { ISI:000347596700001,
	title = {Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets},
	journal = {Journal of Molecular Graphics \& Modelling},
	volume = {54},
	year = {2014},
	month = {NOV},
	pages = {1-9},
	publisher = {ELSEVIER SCIENCE INC},
	address = {360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA},
	abstract = {<p>Vinblastine (VLB), a cytotoxic alkaloid is used extensively against various cancer types and the crystal structure of its tubulin complex is already known. Multitarget affinity of vinblastine has been investigated and the nature of binding with biological receptors namely, duplex DNA and Human serum albumin (HSA) has been compared to the binding characteristics of its known complex with natural high affinity receptor tubulin using molecular docking and QM-MM calculations. VLB is found to interact with DNA as well as HSA protein, though, with weaker affinity as compared to tubulin. Analysis of various docked complexes revealed that the H-bonds and cation-pi bonds do not have significant contribution to the binding interactions and despite its large size, VLB remains in relaxed conformation and fits in the hydrophobic regions on the receptors. (C) 2014 Elsevier Inc. All rights reserved.</p>},
	keywords = {Drug-DNA interactions, Drug-protein binding, Human serum albumin, Molecular docking, Multitarget affinity, QM-MM calculation, Vinblastine},
	issn = {1093-3263},
	doi = {10.1016/j.jmgm.2014.09.001},
	author = {Pandya, Prateek and Agarwal, Lokesh Kr and Gupta, Neelima and Pal, Sourav}
}
@article {47668,
	title = {ZCTs knockdown using antisense LNA GapmeR in specialized photomixotrophic cell suspensions of Catharanthus roseus: Rerouting the flux towards mono and dimeric indole alkaloids},
	journal = {Physiology and Molecular Biology of Plants},
	volume = {27},
	year = {2021},
	month = {JUL},
	pages = {1437-1453},
	type = {Article},
	abstract = {The present study was carried out to silence the transcription factor genes ZCT1, ZCT2 and ZCT3 via lipofectamine based antisense LNA GapmeRs transfection into the protoplasts of established photomixotrophic cell suspensions. The photomixotrophic cell suspensions with a threshold of 0.5\% sucrose were raised and established using two-tiered CO2 providing flasks kept under high light intensity. The photomixotrophic cell suspensions showed morphologically different thick-walled cells under scanning electron microscopic analysis in comparison to the simple thin-walled parenchymatous control cell suspensions. The LC-MS analysis registered the vindoline production (0.0004 +/- 0.0001 mg/g dry wt.) in photomixotrophic cell suspensions which was found to be absent in control cell suspensions. The protoplasts were isolated from the photomixotrophic cell suspensions and subjected to antisense LNA GapmeRs silencing. Three lines, viz. Z1A, Z2C and Z3G were obtained where complete silencing of ZCT1, ZCT2 and ZCT3 genes, respectively, was observed. The Z3G line was found to show maximum production of vindoline (0.038 +/- 0.001 mg/g dry wt.), catharanthine (0.165 +/- 0.008 mg/g dry wt.) and vinblastine (0.0036 +/- 0.0003 mg/g dry wt.). This was supported by the multifold increment in the gene expression of TDC, SLS, STR, SGD, d4h, dat, CrT16H and Crprx. The present work indicates the master regulation of ZCT3 knockdown among all three ZCTs transcription factors in C. roseus to enhance the terpenoid indole alkaloids production. The successful silencing of transcription repressor genes has been achieved in C. roseus plant system by using photomixotrophic cell cultures through GapmeR based silencing. The present study is a step towards metabolic engineering of the TIAs pathway using protoplast transformation in C. roseus.},
	keywords = {Catharanthine, LC-MS, Protoplast, TIAs, Vinblastine, Vindoline},
	issn = {0971-5894},
	doi = {10.1007/s12298-021-01017-y},
	author = {Verma, Priyanka and Khan, Shamshad Ahmad and Parasharami, Varsha and Mathur, Ajay Kumar}
}
