Taxol (Paclitaxel)

undergraduate thesis

• Author: Kristian Subota
• Mentor: Marko Močibob (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2022-09-08, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Taxol (Paclitaxel), tetraciklički diterpen, je sekundarni metabolit biljnog porijekla s antitumorskim
svojstvima kojeg sintetiziraju stabla roda Taxus. Prvi put je izoliran iz kore biljke Taxus baccata
početkom druge polovice 20. stoljeća, skoro nijedan drugi lijek nije zaplijenio pažnju javnosti kao
paclitaxel. Njegov uspjeh u tretmanu mnogo vrsta tumora je od velike važnosti. Veže se na βtubulin i ometa dinamiku mikrotubula inhibirajući njihovu depolimerizaciju, za razliku od ostalih
agensa koji djeluju na mikrotubule, poput vinkristina i vinblastina koji onemogućuju
polimerizaciju. Apoptozu stanica uzrokuje inhibicijom staničnog ciklusa, no i sekundarnim
genetskim mehanizmima. Njegova ekstremno niska prirodna zastupljenost primorala je na traženje
alternativnih puteva proizvodnje poput kulture stanica, bakterijskih kultura, endofita, kompletne
sinteze i polusinteze. Taxol posjeduje vrlo kompleksnu biosintezu koja uključuje više od 19 koraka,
i do danas nisu svi enzimi koji sudjeluju u potpunosti okarakterizirani. Uz to, glavni izazovi za
buduća istraživanja su pronalazak ekonomski isplativog puta proizvodnje Taxola
mikroorganizmima i povećanje biodostupnosti lijeka nanotehnologijom bez negativnih utjecaja na
zdravlje pacijenata.

Abstract (english)

Taxol (Paclitaxel), a tetracyclic diterpene, is a secondary metabolite of plant origin with
antitumoral activity. It is synthesized by trees of the genus Taxus and it was first extracted from
the bark of Taxus baccata in the 1960s, no other drug attracted so much media attention since. Its
success in the treatment of a variety of cancers is of great importance. It binds to β-tubulin and
disrupts the microtubular dynamics through inhibition of their depolymerization, unlike other
microtubule targeting agents like vinblastine and vincristine which disable the polymerization. Cell
apoptosis is caused by the arrest of the cell cycle but also by exerting effects on gene expression.
Its extremely low natural occurence in the yew bark forced the search for alternative production
sources such as harvesting it from cell culture, bacterial cultures, endophytes, total synthesis and
semi-synthesis routes. Taxol has an extremely complicated biosynthesis pathway which has over
19 steps in total, and still today some of the enzymes involved have not been characterized. Besides
that, main challenges for the future development and research include finding an economically
viable microbial way of production, increasing bioavailability of the drug by nanotechnology
without adverse effects on patients health.

• Keywords: antineoplastik; mikrotubuli; apoptoza; karcinom; biosinteza; biotehnologija
• Keywords (english): antineoplastic; microtubules; apoptosis; cancer; biosynthesis; biotechnology
• Language: croatian
• URN:NBN: urn:nbn:hr:217:642009
• Study programme: Title: Ecology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-10-04 09:46:00