Plant cell culture for production of paclitaxel and other taxanes.

Great advances in cell cultures of Taxus spp. for production of Taxol (generic name: paclitaxel) and other taxanes (taxoids) have been achieved in the past decade. This article reviews the manipulation of inducing factors--elicitors, gas composition, osmotic pressure, and conditioned medium; bioprocessing strategies--combining of inducing techniques, two-phase and two-stage cultivation, semi-continuous and perfusion cultures, and feeding of precursors or sugars; and bioreactors and scale-up. Perspectives on a more rational and efficient process involving metabolic engineering are also discussed.

[1]  A. Zeng,et al.  Fungal elicitor-induced cell apoptosis in suspension cultures of Taxus chinensis var. mairei for taxol production , 2002 .

[2]  Jin-Hyun Kim,et al.  Enhanced production of paclitaxel by semi-continuous batch process (SCBP) in suspension culture of Taxus chinensis , 2001 .

[3]  W. Lan,et al.  Oxidative Stress and Taxol Production Induced by Fungal Elicitor in Cell Suspension Cultures of Taxus Chinensis , 2002, Biologia Plantarum.

[4]  Y. Yukimune,et al.  Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures , 1996, Nature Biotechnology.

[5]  H. Pedersen,et al.  Taxol partitioning in two-phase plant cell cultures of Taxus brevifolia , 1996 .

[6]  M. Bonfill,et al.  Improved Paclitaxel and Baccatin III Production in Suspension Cultures of Taxusmedia , 2002, Biotechnology progress.

[7]  A. Fett-Neto,et al.  Improved taxol yield by aromatic carboxylic acid and amino acid feeding to cell cultures of taxus cuspidata , 1994, Biotechnology and bioengineering.

[8]  A. Stierle,et al.  Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. , 1993, Science.

[9]  Robert M. Long,et al.  The final acylation step in Taxol biosynthesis: Cloning of the taxoid C13-side-chain N-benzoyltransferase from Taxus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  K. Ishihara,et al.  Regioselective acylation of flavonoid glucoside with aromatic acid by an enzymatic reaction system from cultured cells of Ipomoea batatas. , 2000, Journal of bioscience and bioengineering.

[11]  W Hu,et al.  Effect of bottom clearance on performance of airlift bioreactor in high-density culture of Panax notoginseng cells. , 2001, Journal of bioscience and bioengineering.

[12]  M. Shuler,et al.  Metabolic Inhibitors, Elicitors, and Precursors as Tools for Probing Yield Limitation in Taxane Production by Taxuschinensis Cell Cultures , 1996, Biotechnology progress.

[13]  R. Croteau,et al.  Molecular cloning of a taxa-4(20),11(12)-dien-5alpha-ol-O-acetyl transferase cDNA from Taxus and functional expression in Escherichia coli. , 2000, Archives of biochemistry and biophysics.

[14]  D. Ettinger,et al.  Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. , 1989 .

[15]  J. Memelink,et al.  Metabolic engineering of plant secondary metabolite pathways for the production of fine chemicals , 1999, Biotechnology Letters.

[16]  jae-hwa Lee,et al.  Effects of osmotic pressure on production of recombinant human granulocyte-macrophage colony stimulating factor in plant cell suspension culture , 2002 .

[17]  V. Bisaria,et al.  Bioprocess considerations for production of secondary metabolites by plant cell suspension cultures , 2002 .

[18]  J. Linden,et al.  Gas concentration effects on secondary metabolite production by plant cell cultures. , 2001, Advances in biochemical engineering/biotechnology.

[19]  A. P. Jackman,et al.  Ribosome‐Inactivating Protein Production from Trichosanthes kirilowii Plant Cell Cultures , 1994 .

[20]  S Furusaki,et al.  Taxol (paclitaxel) production using free and immobilized cells of Taxus cuspidata. , 1997, Biotechnology and bioengineering.

[21]  J. Linden,et al.  Kinetic Studies of Paclitaxel Production by Taxus canadensis Cultures in Batch and Semicontinuous with Total Cell Recycle , 1999, Biotechnology progress.

[22]  Chuangui Wang,et al.  Enhancement of Taxol production and excretion in Taxus chinensis cell culture by fungal elicitation and medium renewal , 2001, Applied Microbiology and Biotechnology.

[23]  Zhen-yu Wang,et al.  Combination of conditioned medium and elicitation enhances taxoid production in bioreactor cultures of Taxus chinensis cells , 2002 .

[24]  R. Croteau,et al.  Cloning and functional expression of a cDNA encoding geranylgeranyl diphosphate synthase from Taxus canadensis and assessment of the role of this prenyltransferase in cells induced for taxol production. , 1998, Archives of biochemistry and biophysics.

[25]  M. Kino‐oka,et al.  Characterization and application of plant hairy roots endowed with photosynthetic functions. , 2001, Advances in biochemical engineering/biotechnology.

[26]  Saurabh Chattopadhyay,et al.  Production of podophyllotoxin by plant cell cultures of Podophyllum hexandrum in bioreactor. , 2002, Journal of bioscience and bioengineering.

[27]  J. Pezzuto.  Taxol production in plant cell culture comes of age , 1996, Nature Biotechnology.

[28]  R. Cella,et al.  Current Issues in Plant Molecular and Cellular Biology , 1995, Current Plant Science and Biotechnology in Agriculture.

[29]  H. Aoyagi,et al.  Efficient paclitaxel production using protoplasts isolated from cultured cells of Taxus cuspidata. , 2002, Planta medica.

[30]  V. Gomord,et al.  Expression of a carrot invertase gene in tobacco suspension cells cultivated in batch and continuous culture conditions. , 1999, Journal of bioscience and bioengineering.

[31]  X. Mei,et al.  Enhanced Taxol Production and Release in Taxus chinensisCell Suspension Cultures with Selected Organic Solvents and Sucrose Feeding , 2001, Biotechnology progress.

[32]  J. Zhong,et al.  Biochemical engineering of the production of plant-specific secondary metabolites by cell suspension cultures. , 2001, Advances in biochemical engineering/biotechnology.

[33]  Pan,et al.  Scale-up study on suspension cultures of Taxus chinensis cells for production of taxane diterpene. , 2000, Enzyme and microbial technology.

[34]  A. McPhail,et al.  Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. , 1971, Journal of the American Chemical Society.

[35]  G. Theodoridis,et al.  Induction of geranylgeranyl diphosphate synthase activity and taxane accumulation in Taxus baccata cell cultures after elicitation by methyl jasmonate , 1999 .

[36]  Zhen-yu Wang,et al.  Repeated elicitation enhances taxane production in suspension cultures of Taxus chinensis in bioreactors , 2002, Biotechnology Letters.

[37]  Yu Shen,et al.  Development of a bioreactor operation strategy for L-DOPA production using Stizolobium hassjoo suspension culture , 2002 .

[38]  X. Mei,et al.  Stimulation of taxol production and excretion in Taxus spp cell cultures by rare earth chemical lanthanum. , 2001, Journal of biotechnology.

[39]  N. Jin,et al.  Cloning and expression of the external‐glycoprotein gene mutant from HIV‐2 in the methylotrophic yeast Pichia pastoris and identification of the glycoprotein , 2001, Biotechnology and applied biochemistry.

[40]  Hong,et al.  Enhancement of paclitaxel production by temperature shift in suspension culture of Taxus chinensis. , 2000, Enzyme and microbial technology.

[41]  H. Lucas.  Ueber ein in den Blättern von Taxus baccata L. enthaltenes Alkaloid (das Taxin) , 1856 .

[42]  D. Gibson,et al.  Initiation and growth of cell lines of Taxus brevifolia (Pacific yew) , 1993, Plant Cell Reports.

[43]  E. Wickremesinhe,et al.  Taxus callus cultures: Initiation, growth optimization, characterization and taxol production , 1993, Plant Cell, Tissue and Organ Culture.

[44]  M. Shuler,et al.  Elicitation of Taxus sp. cell cultures for production of taxol , 1995, Biotechnology Letters.

[45]  Susan C. Roberts,et al.  Kinetics of taxol production and nutrient use in suspension cultures of Taxus cuspidata in shake flasks and a Wilson-type bioreactor. , 1996, Enzyme and microbial technology.

[46]  S -I. Kim,et al.  Effect of osmotic pressure on paclitaxel production in suspension cell cultures of Taxus chinensis. , 2001, Enzyme and microbial technology.

[47]  Hyung-Kyoon Choi,et al.  Mass Production of Paclitaxel by Plant Cell Culture , 2002 .

[48]  J. Linden,et al.  Gas phase composition effects on suspension cultures of Taxus cuspidata , 1995, Biotechnology and bioengineering.

[49]  Y. Yoo,et al.  Enhancement of taxol production by in situ recovery of product , 1998 .

[50]  J. Zhong,et al.  Significant improvement of taxane production in suspension cultures of Taxus chinensis by combining elicitation with sucrose feed , 2001 .

[51]  Yingjin Yuan,et al.  A double oxidative burst for taxol production in suspension cultures of Taxus chinensis var. mairei induced by oligosaccharide from Fusarium oxysprum , 2002 .

[52]  P. Doran,et al.  Design of Mixing Systems for Plant Cell Suspensions in Stirred Reactors , 1999, Biotechnology progress.

[53]  Wenyuan Gao,et al.  Jasmonic acid improves ginsenoside accumulation in adventitious root culture of Panax ginseng C.A. Meyer , 2002 .

[54]  M. Shuler,et al.  Taxol production in bioreactors: Kinetics of biomass accumulation, nutrient uptake, and taxol production by cell suspensions of Taxus baccata , 1995, Biotechnology and bioengineering.

[55]  H. Kurata,et al.  Screening for transgenic plant cells that highly express a target gene from genetically mixed cells , 2002 .

[56]  S. Byun,et al.  Integrated bioprocessing for plant cell cultures. , 2001, Advances in biochemical engineering/biotechnology.

[57]  J. Zhong,et al.  Enhanced taxane productivity in bioreactor cultivation of Taxus chinensis cells by combining elicitation, sucrose feeding and ethylene incorporation , 2002 .

[58]  J. Linden,et al.  Methyl Jasmonate Induced Production of Taxol in Suspension Cultures of Taxus cuspidata: Ethylene Interaction and Induction Models , 1996, Biotechnology progress.

[59]  Š. Baebler,et al.  Jasmonic acid stimulates taxane production in cell suspension culture of yew (Taxus x media). , 2002, Planta Medica.

[60]  S. Jennewein,et al.  Taxol: biosynthesis, molecular genetics, and biotechnological applications , 2001, Applied Microbiology and Biotechnology.

[61]  J. Zhong,et al.  Manipulation of ginsenoside heterogeneity in cell cultures of Panax notoginseng by addition of jasmonates. , 2002, Journal of bioscience and bioengineering.

[62]  Hyung-Kyoon Choi,et al.  Intermittent maltose feeding enhances paclitaxel production in suspension culture of Taxus chinensis cells , 2000, Biotechnology Letters.

[63]  R. Arteca,et al.  Methodology for the identification and purification of taxol and cephalomannine from Taxus callus cultures , 1993 .

[64]  Jian-Jiang Zhong,et al.  Effect of mixing time on taxoid production using suspension cultures of Taxus chinensis in a centrifugal impeller bioreactor. , 2002, Journal of bioscience and bioengineering.

[65]  H. Honda,et al.  In situ regeneration of rice (Oryza sativa L.) callus immobilized in polyurethane foam. , 2001, Journal of bioscience and bioengineering.

[66]  P. Schiff,et al.  Promotion of microtubule assembly in vitro by taxol , 1979, Nature.

[67]  C. Fairchild,et al.  Synthesis and antitumor activity of novel C-7 paclitaxel ethers: discovery of BMS-184476. , 2001, Journal of medicinal chemistry.

[68]  H. Hamada,et al.  Taxus sp. cell, tissue and organ cultures as alternative sources for taxoids production: a literature survey , 1996, Plant Cell, Tissue and Organ Culture.

[69]  A. Alfermann,et al.  Taxol® and baccatin III production in suspension cultures of Taxus baccata and Taxus wallichiana in an airlift bioreactor , 2002 .

[70]  Huibi Xu,et al.  Effects of salicylic acid on fungal elicitor-induced membrane-lipid peroxidation and taxol production in cell suspension cultures of Taxus chinensis , 2001 .

[71]  A. Canaguier,et al.  Production of taxoids with biological activity by plants and callus culture from selected Taxus genotypes. , 2002, Phytochemistry.

[72]  J. Zhong,et al.  A novel centrifugal impeller bioreactor. I. Fluid circulation, mixing, and liquid velocity profiles , 2000, Biotechnology and bioengineering.

[73]  Jian-Jiang Zhong,et al.  Significant improvement of taxane production in suspension cultures of Taxus chinensis by sucrose feeding strategy , 1999 .

[74]  J. Zhong,et al.  A novel centrifugal impeller bioreactor. II. Oxygen transfer and power consumption , 2000, Biotechnology and bioengineering.

[75]  W. Reynolds,et al.  Cell Culture of Taxus as a Source of the Antineoplastic Drug Taxol and Related Taxanes , 1992, Bio/Technology.

[76]  S. Rao,et al.  Plant cell cultures: Chemical factories of secondary metabolites. , 2002, Biotechnology advances.

[77]  M. Terashima,et al.  Effect of osmotic pressure on human α1-antitrypsin production by plant cell culture , 1999 .

[78]  Xiaolei Tang,et al.  Selective cytotoxicity of scFv-TNF fusion protein on the tumor cells , 2002, Biotechnology Letters.

[79]  Wu,et al.  Kinetics of two-liquid-phase Taxus cuspidata cell culture for production of Taxol. , 2000, Biochemical engineering journal.

[80]  S. H. Son,et al.  Large-scale growth and taxane production in cell cultures of Taxus cuspidata (Japanese yew) using a novel bioreactor , 2000, Plant Cell Reports.

[81]  M. Shuler,et al.  The kinetics of taxoid accumulation in cell suspension cultures of Taxus following elicitation with methyl jasmonate. , 1999, Biotechnology and bioengineering.

[82]  Wei Zhang,et al.  Towards manipulation of post-biosynthetic events in secondary metabolism of plant cell cultures , 2002 .