Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

Codruta Ignea; Marianna Pontini; Mohammed S. Motawia; Massimo E Maffei; Antonios M Makris; Sotirios C. Kampranis

doi:10.1038/s41589-018-0166-5

Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

Codruta Ignea, Marianna Pontini, Mohammed S. Motawia, Massimo E Maffei, Antonios M Makris, Sotirios C. Kampranis

28 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Chemical Biology
Vol/bind	14
Udgave nummer	12
Sider (fra-til)	1090-1098
Antal sider	9
ISSN	1552-4450
DOI	https://doi.org/10.1038/s41589-018-0166-5
Status	Udgivet - 1 dec. 2018

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Citationsformater

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AU - Ignea, Codruta

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AU - Motawia, Mohammed S.

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AU - Makris, Antonios M

AU - Kampranis, Sotirios C.

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AB - 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.

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Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

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