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.
