Terpenoids constitute the largest, most diverse group of natural products with numerous ones garnering commercial and medicinal interest. Most terpenoids are naturally produced in low amounts so their purification suffers from low yields and consumption of large amounts of natural resources. Hence, the extinction of the natural source becomes a real threat and the amount of isolated compound usually cannot cover market demand especially for medicinally important compounds like anticancer paclitaxel and antimalarial artemisinin. Also, synthesis of most terpenoids is problematic and expensive due to the complexity of their structures. Thus, the need for alternate methods of terpenoid production is a pressing issue. Among these methods is the microbial production of terpenoids, which has been researched in the last few decades. The objectives of the thesis by Ingy Abdallah are establishing the Gram-positive bacterium Bacillus subtilis as a platform organism for terpenoid production by understanding and improving the biosynthetic routes of terpenoids including the core enzymes involved in the process such as terpene synthases. A B. subtilis strain overexpressing the terpenoid biosynthetic pathway was successfully engineered then used for the production of C30 carotenoids and the diterpene precursor of paclitaxel, taxadiene. This strain can serve as a cell factory for production of various terpenoids. In addition, the research in this thesis delved into the enzyme family of terpene synthases, which are essential for the formation of terpenoids. The focus was on understanding the structure-function relations of amorphadiene synthase, a key enzyme in artemisinin production, and improving its catalytic activity.
|Translated title of the contribution||Een cel-fabriek voor terpenen|
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2018|