Synthesis of Non-Canonical Terpenoids in Yeast

One application of synthetic biology is the re-design of existing biological systems to acquire new functions. In this context, expanding the chemical code underlying key biosynthetic pathways will lead to the synthesis of compounds with new structures and potentially new biological activities. Terpenoids are the largest group of specialized metabolites with numerous applications. Yet, being synthesized from 5-carbon units, they are restricted to distinct classes that differ by 5 carbon atoms (C10, C15, C20, etc.). To expand the diversity of terpenoid structures, we engineered yeast cells to synthesize a non-canonical building block with 11 carbons and produced 40 C11 terpene scaffolds that can form the basis for an entire terpenoid class. By identifying a single-residue switch that converts C10 plant monoterpene synthases to C11-specific enzymes, we engineered dedicated synthases for C11 terpene production. This approach will enable the systematic expansion of the chemical space accessed by terpenoids.

Reference:

Ignea, C., Pontini, M., Motawia, M. S., Maffei, M. E., Makris, A. M. & Kampranis, S. C. (2018) Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering, Nature Chemical Biology, 14, 1090-98.