Dataset Information

Multi-Substrate Terpene Synthases: Their Occurrence and Physiological Significance.

ABSTRACT: Terpene synthases are responsible for synthesis of a large number of terpenes in plants using substrates provided by two distinct metabolic pathways, the mevalonate-dependent pathway that is located in cytosol and has been suggested to be responsible for synthesis of sesquiterpenes (C15), and 2-C-methyl-D-erythritol-4-phosphate pathway located in plastids and suggested to be responsible for the synthesis of hemi- (C5), mono- (C10), and diterpenes (C20). Recent advances in characterization of genes and enzymes responsible for substrate and end product biosynthesis as well as efforts in metabolic engineering have demonstrated existence of a number of multi-substrate terpene synthases. This review summarizes the progress in the characterization of such multi-substrate terpene synthases and suggests that the presence of multi-substrate use might have been significantly underestimated. Multi-substrate use could lead to important changes in terpene product profiles upon substrate profile changes under perturbation of metabolism in stressed plants as well as under certain developmental stages. We therefore argue that multi-substrate use can be significant under physiological conditions and can result in complicate modifications in terpene profiles.

SUBMITTER: Pazouki L

PROVIDER: S-EPMC4940680 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-Substrate Terpene Synthases: Their Occurrence and Physiological Significance.

Pazouki Leila L Niinemets Ülo Ü

Frontiers in plant science 20160712

Terpene synthases are responsible for synthesis of a large number of terpenes in plants using substrates provided by two distinct metabolic pathways, the mevalonate-dependent pathway that is located in cytosol and has been suggested to be responsible for synthesis of sesquiterpenes (C15), and 2-C-methyl-D-erythritol-4-phosphate pathway located in plastids and suggested to be responsible for the synthesis of hemi- (C5), mono- (C10), and diterpenes (C20). Recent advances in characterization of gen ...[more]

PMID: 27462341

Similar Datasets

Project description:The magnificent chemodiversity of more than 95 000 terpenoid natural products identified to date largely originates from catalysis by two types of terpene synthases, prenyltransferases and cyclases. Prenyltransferases utilize 5-carbon building blocks in processive chain elongation reactions to generate linear C5n isoprenoid diphosphates (n ≥ 2), which in turn serve as substrates for terpene cyclases that convert these linear precursors into structurally complex hydrocarbon products containing multiple rings and stereocenters. Terpene cyclization reactions are the most complex organic transformations found in nature in that more than half of the substrate carbon atoms undergo changes in chemical bonding during a multistep reaction sequence proceeding through several carbocation intermediates. Two general classes of cyclases are established on the basis of the chemistry of initial carbocation formation, and structural studies from our laboratory and others show that three fundamental protein folds designated α, β, and γ govern this chemistry. Catalysis by a class I cyclase occurs in an α domain, where a trinuclear metal cluster activates the substrate diphosphate leaving group to generate an allylic cation. Catalysis by a class II cyclase occurs in a β domain or at the interface of β and γ domains, where an aspartic acid protonates the terminal π bond of the substrate to yield a tertiary carbocation. Crystal structures reveal domain architectures of α, αβ, αβγ, βγ, and β.In some terpene synthases, these domains are combined to yield bifunctional enzymes that catalyze successive biosynthetic steps in assembly line fashion. Structurally characterized examples include bacterial geosmin synthase, an αα domain enzyme that catalyzes a class I cyclization reaction of C15 farnesyl diphosphate in one active site and a transannulation-fragmentation reaction in the other to yield C12 geosmin and C3 acetone products. In comparison, plant abietadiene synthase is an αβγ domain enzyme in which C20 geranylgeranyl diphosphate undergoes tandem class II-class I cyclization reactions to yield the tricyclic product. Recent structural studies from our laboratory show that bifunctional fungal cyclases form oligomeric complexes for assembly line catalysis. Bifunctional (+)-copalyl diphosphate synthase adopts (αβγ)6 architecture in which the α domain generates geranylgeranyl diphosphate, which then undergoes class II cyclization in the βγ domains to yield the bicyclic product. Bifunctional fusicoccadiene synthase adopts (αα)6 or (αα)8 architecture in which one α domain generates geranylgeranyl diphosphate, which then undergoes class I cyclization in the other α domain to yield the tricyclic product. The prenyltransferase α domain mediates oligomerization in these systems. Attached by flexible polypeptide linkers, cyclase domains splay out from oligomeric prenyltransferase cores.In this Account, we review structure-function relationships for these bifunctional terpene synthases, with a focus on the oligomeric systems studied in our laboratory. The observation of substrate channeling for fusicoccadiene synthase suggests a model for dynamic cluster channeling in catalysis by oligomeric assembly line terpenoid synthases. Resulting efficiencies in carbon management suggest that such systems could be particularly attractive for use in synthetic biology approaches to generate high-value terpenoid natural products.

Dataset Information

Multi-Substrate Terpene Synthases: Their Occurrence and Physiological Significance.

Publications

Multi-Substrate Terpene Synthases: Their Occurrence and Physiological Significance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets