Increased paclitaxel recovery from Taxus baccata vascular stem cells using novel in situ product recovery approaches

Jorge H. Santoyo-Garcia; Marissa Valdivia-Cabrera; Marisol Ochoa-Villarreal; Samuel Casasola-Zamora; Magdalena Ripoll; Ainoa Escrich; Elisabeth Moyano; Lorena Betancor; Karen J. Halliday; Gary J. Loake; Leonardo Rios-Solis

doi:10.1186/s40643-023-00687-8

Bioresources and Bioprocessing ›› 2023, Vol. 10 ›› Issue (1) : 68 DOI: 10.1186/s40643-023-00687-8

Research

Increased paclitaxel recovery from Taxus baccata vascular stem cells using novel in situ product recovery approaches

Author information +

¹ Institute for Bioengineering, School of Engineering, University of Edinburgh, King’s Buildings, EH9 3FB, Edinburgh, UK

² Centre for Engineering Biology, University of Edinburgh, King’s Buildings, EH9 3BF, Edinburgh, UK

³ Institute of Molecular Plant Sciences, School of Biological Sciences, University of Edinburgh, King’s Buildings, EH9 3BF, Edinburgh, UK

⁴ Green Bioactives, Douglas House, Pentland Science Park, Midlothian, EH16 0PL, UK

⁵ School of Natural and Environmental Sciences, Molecular Biology and Biotechnology Division, Newcastle University, NE1 7RU, Newcastle upon Tyne, UK

⁶ Laboratorio de Biotecnología, Universidad ORT Uruguay, Mercedes 1237, 11100, Montevideo, Uruguay

⁷ Graduate Program in Chemistry, Facultad de Química, Universidad de la República, Montevideo, Uruguay

⁸ Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003, Barcelona, Spain

⁹ Department of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Gower Street, WC1E 6BT, London, UK

^a jorge.santoyogarcia@roslintech.com

^m leo.rios@ucl.ac.uk

Show less

History +

PDF

Abstract

In this study, several approaches were tested to optimise the production and recovery of the widely used anticancer drug Taxol^® (paclitaxel) from culturable vascular stem cells (VSCs) of Taxus baccata, which is currently used as a successful cell line for paclitaxel production. An in situ product recovery (ISPR) technique was employed, which involved combining three commercial macro-porous resin beads (HP-20, XAD7HP and HP-2MG) with batch and semi-continuous cultivations of the T. baccata VSCs after adding methyl jasmonate (Me-JA) as an elicitor. The optimal resin combination resulted in 234 ± 23 mg of paclitaxel per kg of fresh-weight cells, indicating a 13-fold improved yield compared to the control (with no resins) in batch cultivation. This resin treatment was further studied to evaluate the resins’ removal capacity of reactive oxygen species (ROS), which can cause poor cell growth or reduce product synthesis. It was observed that the ISPR cultivations had fourfold less intracellular ROS concentration than that of the control; thus, a reduced ROS concentration established by the resin contributed to increased paclitaxel yield, contrary to previous studies. These paclitaxel yields are the highest reported to date using VSCs, and this scalable production method could be applied for a diverse range of similar compounds utilising plant cell culture.

Keywords

Paclitaxel / In situ product recovery / Vascular stem cells / Taxus baccata / Reactive oxygen species

Cite this article

Download citation ▾

Jorge H. Santoyo-Garcia, Marissa Valdivia-Cabrera, Marisol Ochoa-Villarreal, Samuel Casasola-Zamora, Magdalena Ripoll, Ainoa Escrich, Elisabeth Moyano, Lorena Betancor, Karen J. Halliday, Gary J. Loake, Leonardo Rios-Solis. Increased paclitaxel recovery from Taxus baccata vascular stem cells using novel in situ product recovery approaches. Bioresources and Bioprocessing, 2023, 10(1): 68 DOI:10.1186/s40643-023-00687-8

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Abhishek S, Elah P. Espada J. Fluorescence detection of increased reactive oxygen species levels in Saccharomyces cerevisiae at the diauxic shift. Reactive oxygen species methods and protocols, 2021, New York: Humana, 81-91.

[2]	Ballatore C, Hyde E, Deiches RF, . Paclitaxel C-10 carbamates: potential candidates for the treatment of neurodegenerative tauopathies. Bioorganic Med Chem Lett, 2007, 17: 3642-3646.

[3]	Bentebibel S, Moyano E, Palazón J, . Effects of immobilization by entrapment in alginate and scale-up on paclitaxel and baccatin III production in cell suspension cultures of Taxus baccata. Biotechnol Bioeng, 2005, 89: 647-655.

[4]	Bian G, Yuan Y, Tao H, . Production of taxadiene by engineering of mevalonate pathway in Escherichia coli and endophytic fungus Alternaria alternata TPF6. Biotechnol J, 2017, 12: 1-11.

[5]	Brennan TCR, Turner CD, Krömer JO, Nielsen LK. Alleviating monoterpene toxicity using a two-phase extractive fermentation for the bioproduction of jet fuel mixtures in Saccharomyces cerevisiae. Biotechnol Bioeng, 2012, 109: 2513-2522.

[6]	Cusido RM, Onrubia M, Sabater-Jara AB, . A rational approach to improving the biotechnological production of taxanes in plant cell cultures of Taxus spp. Biotechnol Adv, 2014, 32: 1157-1167.

[7]	Dalmaris E, Multari S, Xanthopoulou A, Avramidou EV, Mansuero D, Martens S, Aravanopoulos FA. Targeted LC-MS/MS analysis for the quantification of taxanes: assessment of chemodiversity in different European yew (Taxus baccata) populations from Greece. Planta Med, 2019, 85: 116.

[8]	Dalmaris E, Avramidou EV, Xanthopoulou A, Aravanopoulos FA. Dataset of targeted metabolite analysis for five taxanes of hellenic Taxus baccata L. populations. Data, 2020, 5: 6-11.

[9]	El-Sayed ESR, Ahmed AS, Hassan IA, . Strain improvement and immobilization technique for enhanced production of the anticancer drug paclitaxel by Aspergillus fumigatus and Alternaria tenuissima. Appl Microbiol Biotechnol, 2019, 103: 8923-8935.

[10]	Gai QY, Jiao J, Wang X, . Simultaneous determination of taxoids and flavonoids in twigs and leaves of three Taxus species by UHPLC-MS/MS. J Pharm Biomed Anal, 2020, 189: 113456.

[11]	Gamborg OL, Miller RA, Ojima K. Nutrient requirements of soybean of suspension. Exp Cell Res, 1968, 158: 151-158.

[12]	Han RB, Yuan YJ. Oxidative burst in suspension culture of Taxus cuspidata induced by a laminar shear stress in short-term. Biotechnol Prog, 2004, 20: 507-513.

[13]	Hirasuna TJ, Pestchanker LJ, Srinivasan V, Shuler ML. Taxol production in suspension cultures of Taxus baccata. Plant Cell Tissue Organ Cult, 1996, 44: 95-102.

[14]	Howat S, Park B, Oh IS, . Paclitaxel: biosynthesis, production and future prospects. N Biotechnol, 2014, 31: 242-245.

[15]	Jiang M, Stephanopoulos G, Pfeifer BA. Downstream reactions and engineering in the microbially reconstituted pathway for Taxol. Appl Microbiol Biotechnol, 2012, 94: 841-849.

[16]	Jiang H, Zhang XW, Liao QL, . Electrochemical monitoring of paclitaxel-induced ROS release from mitochondria inside single cells. Small, 2019, 15: 1-5.

[17]	Kampan NC, Madondo MT, McNally OM, . Paclitaxel and its evolving role in the management of ovarian cancer. Biomed Res Int, 2015, 15: 21.

[18]	Kang DY, Kim JH. Ultrasonic cavitation bubble- and gas bubble-assisted adsorption of paclitaxel from Taxus chinensis onto Sylopute. Korean J Chem Eng, 2021, 38: 2286-2293.

[19]	Kim YS, Kim JH. Isotherm, kinetic and thermodynamic studies on the adsorption of paclitaxel onto Sylopute. J Chem Thermodyn, 2019, 130: 104-113.

[20]	Kusari S, Singh S, Jayabaskaran C. Rethinking production of Taxol® (paclitaxel) using endophyte biotechnology. Trends Biotechnol, 2014, 32: 304-311.

[21]	Kwon IC, Yoo YJ, Lee JH, Hyun JO. Enhancement of taxol production by in situ recovery of product. Process Biochem, 1998, 33: 701-707.

[22]	Lee EK, Jin YW, Park JH, . Cultured cambial meristematic cells as a source of plant natural products. Nat Biotechnol, 2010, 28: 1213-1217.

[23]	Liu SR, Yang XJ, Sun DF. Enhanced production of ε-poly-l-lysine by immobilized Streptomyces ahygroscopicus through repeated-batch or fed-batch fermentation with in situ product removal. Bioprocess Biosyst Eng, 2021, 44: 2109-2120.

[24]	Malik S, Cusidó RM, Mirjalili MH, . Production of the anticancer drug taxol in Taxus baccata suspension cultures: a review. Process Biochem, 2011, 46: 23-34.

[25]	Min H, Kim J. Process synthesis and optimization for the isolation and purification of paclitaxel from Taxus chinensis. Korean J Chem Eng, 2022, 39: 3389-3398.

[26]	Montero P, Pérez-Leal M, Pérez-Fidalgo JA, . Paclitaxel induces epidermal molecular changes and produces subclinical alterations in the skin of gynecological cancer patients. Cancers, 2022, 14: 1146.

[27]	Naill MC, Kolewe ME, Roberts SC. Paclitaxel uptake and transport in Taxus cell suspension cultures. Biochem Eng J, 2012, 63: 50-56.

[28]	Najmi Z, Ebrahimipour G, Franzetti A, Banat IM. In situ downstream strategies for cost-effective bio/surfactant recovery. Biotechnol Appl Biochem, 2018, 65: 523-532.

[29]	Nowrouzi B, Rios-Solis L. Redox metabolism for improving whole-cell P450-catalysed terpenoid biosynthesis. Crit Rev Biotechnol, 2021, 42: 1213-1237.

[30]	Nowrouzi B, Li RA, Walls LE, . Enhanced production of taxadiene in Saccharomyces cerevisiae. Microb Cell Fact, 2020, 19: 1-12.

[31]	Nowrouzi B, Lungang L, Rios-Solis L. Exploring optimal Taxol® CYP725A4 activity in Saccharomyces cerevisiae. Microb Cell Fact, 2022, 21: 1-24.

[32]	Ochoa-Villarreal M, Howat S, SunMi H, . Plant cell culture strategies for the production of natural products. BMB Rep, 2016, 49: 149-158.

[33]	Onrubia M, Moyano E, Bonfill M, . Coronatine, a more powerful elicitor for inducing taxane biosynthesis in Taxus media cell cultures than methyl jasmonate. J Plant Physiol, 2013, 170: 211-219.

[34]	Phillips T, Chase M, Wagner S, . Use of in situ solid-phase adsorption in microbial natural product fermentation development. Ind Microbiol Biotechnol, 2013, 40: 411-425.

[35]	Precedence Research (2022) Paclitaxel injection market size, share, report 2022–2030. In: Healthcare. https://www.precedenceresearch.com/paclitaxel-injection-market. Accesed 31 Oct 2022

[36]	Pyo SH, Song BK, Ju CH, . Effects of absorbent treatment on the purification of paclitaxel from cell cultures of Taxus chinensis and yew tree. Process Biochem, 2005, 40: 1113-1117.

[37]	Santoyo-Garcia JH, Walls LE, Nowrouzi B, . In situ solid-liquid extraction enhances recovery of taxadiene from engineered Saccharomyces cerevisiae cell factories. Sep Purif Technol, 2022, 290: 120880.

[38]

Santoyo-Garcia JH, Walls LE, Valdivia-Cabrera M, . The synergetic effect from the combination of different adsorption resins in batch and semi-continuous cultivations of S. cerevisiae cell factories to produce acetylated Taxanes precursors of the anticancer drug Taxol. Biotechnol Bioeng, 2023, 120: 2160-2174.

[39]	Shi ZD, Yuan YJ, Wu JC, Shang GM. Biological responses of suspension cultures of Taxus chinensis var. mairei to Shear stresses in the short term. Appl Biochem Biotechnol Part A Enzym Eng Biotechnol, 2003, 110: 61-74.

[40]	Shiozaki AA, Senra T, Morikawa AT, . Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles. Clinics, 2016, 71: 435-439.

[41]	Soto ML, Conde E, González-lópez N, . Recovery and concentration of antioxidants from winery wastes. Molecules, 2012, 17: 3008-3024.

[42]	Teworte S, Malcı K, Walls LE, . Recent advances in fed-batch microscale bioreactor design. Biotechnol Adv, 2022, 55: 107888.

[43]	Walls LE, Malci K, Nowrouzi B, . Optimizing the biosynthesis of oxygenated and acetylated Taxol precursors in Saccharomyces cerevisiae using advanced bioprocessing strategies. Biotechnol Bioeng, 2020, 118: 279-293.

[44]	Walls LE, Martinez JL, del Rio Chanona EA, Rios-Solis L. Definitive screening accelerates Taxol biosynthetic pathway optimization and scale up in Saccharomyces cerevisiae cell factories. Biotechnol J, 2022, 17: 2100414.

[45]	Walls LE, Martinez JL, Rios-Solis L. Enhancing Saccharomyces cerevisiae Taxane biosynthesis and overcoming nutritional stress-induced pseudohyphal growth. Microorganisms, 2022, 10: 163.

[46]	Wang YF, Shi QW, Dong M, . Natural taxanes: developments since 1828. Chem Rev, 2011, 111: 7652-7709.

[47]	Wang S, Li C, Wang H, . Effect of elicitors, precursors and metabolic inhibitors on paclitaxel production by Taxus cuspidata cell culture. J for Res, 2016, 27: 1257-1263.

[48]	Weaver BA. How Taxol/paclitaxel kills cancer cells. Mol Biol Cell, 2014, 25: 2677-2681.

[49]	Wilk P, Halim M, Rios-Solis L. El-Mansi EMT, Bryce CFA, Dahhou B, Sanchez S, Demain AL, Allman AR. Recent advances and impacts of microtiter plate-based fermentations in synthetic biology and bioprocess development. Fermentation microbiology and biotechnology, 2019, 4, Boca Raton: CRC Press, 14.

[50]	Yin DM, Wu JC, Yuan YJ. Reactive oxygen species, cell growth, and taxol production of Taxus cuspidata cells immobilized on polyurethane foam. Appl Biochem Biotechnol, 2005, 127: 173-185.

[51]	Yukimune Y, Tabata H, Higashi Y, Hara Y. Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures. Nature, 1996, 14: 1129-1132.

[52]	Zainuddin MF, Fai CK, Ariff AB, . Current pretreatment/cell disruption and extraction methods used to improve intracellular lipid recovery from oleaginous yeasts. Microorganisms, 2021, 9: 1-28.