Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering.
Nat Chem Biol
; 14(12): 1090-1098, 2018 12.
Article
in En
| MEDLINE
| ID: mdl-30429605
ABSTRACT
One application of synthetic biology is the redesign 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 a large group of specialized metabolites with numerous applications. Yet, being synthesized from five-carbon units, they are restricted to distinct classes that differ by five carbon atoms (C10, C15, C20, etc.). To expand the diversity of terpenoid structures, we engineered yeast cells to synthesize a noncanonical 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.
Full text:
1
Database:
MEDLINE
Main subject:
Saccharomyces cerevisiae
/
Terpenes
/
Alkyl and Aryl Transferases
/
Metabolic Engineering
Language:
En
Journal:
Nat Chem Biol
Journal subject:
BIOLOGIA
/
QUIMICA
Year:
2018
Type:
Article
Affiliation country:
Denmark