Engineering the biosynthesis of artemisinin | Abstract
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Journal of Computational Methods in Molecular Design


Engineering the biosynthesis of artemisinin

Author(s): Wim J Quax

Terpenoids represent the largest class of natural products with a diverse array of structures and functions. Many

terpenoids have reported therapeutic properties such as antimicrobial, anti-inflammatory, immunomodulatory and

Chemotherapeutic properties making them of great interest in the medical field. Terpenoids suffer from low natural

yields and complicated chemical synthesis; hence there is a need for a more sustainable production method.

Metabolic engineering using biosynthetic mevalonate and non-mevalonate pathways provides an excellent

opportunity to construct microbial cell factories producing terpenoids. The complexity and diversity of terpenoid

structures depends mainly on the action of the terpene synthases responsible for their synthesis. Amorpha- 4, 11-

diene synthase (ADS) cyclizes the substrate farnesyl pyrophosphate to produce amorpha- 4, 11-diene as the major

product. This is considered the first committed and rate-limiting step in the biosynthesis of the antimalarial

artemisinin. Here, we utilize a reported 3D model of ADS to perform mutability landscape guided enzyme engineering.