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

Pazouki L, Niinemets Ü - Front Plant Sci (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Physiology, Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences Tartu, Estonia.

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.

No MeSH data available.


Related in: MedlinePlus

Terpene biosynthetic pathways and their subcellular compartmentalization in plants. Thick arrows denote the classical understanding of terpenoid synthesis compartmentalization among cytosol and plastid (Bohlmann et al., 1998b; Chen et al., 2011; Tholl and Lee, 2011), reflecting the circumstance that monoterpene and diterpene synthases harboring a chloroplast-targeting peptide are functionally active in plastids and sesquiterpene synthases lacking the target peptide are active in cytosol. However, recent findings of the capacity for multi-substrate use of several mono, sesqui-, and, diterpene synthases suggest that when substrate becomes available, several cytosolic “sesquiterpene” synthases could also operate as monoterpene synthases, and analogously, multi-substrate “monoterpene” and “diterpene” synthases could operate as sesquiterpene synthases in plastids (denoted by thin arrows). In addition, terpenoid synthesis can also potentially occur in mitochondria (Nagegowda, 2010; Tholl and Lee, 2011; Dong et al., 2016). For instance, targeting linalool/(E)-nerolidol synthase (FaNES1) from Fragaria ananassa (Table 1 for protein specifics) to the mitochondria led to the production of (E)-nerolidol and homoterpene 4,8-dimethyl nona-1,3,7-triene (DMNT) in transgenic Arabidopsis thaliana plants (Kappers et al., 2005). DMADP, dimethylallyl diphosphate (C5); MEP pathway, 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway; IDP, isopentenyl diphosphate (C5); FDP, farnesyl diphosphate (C15); GDP, geranyl diphosphate (C10); GGDP, geranylgeranyl diphosphate (C20); NDP, neryl diphosphate (C10).
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Figure 1: Terpene biosynthetic pathways and their subcellular compartmentalization in plants. Thick arrows denote the classical understanding of terpenoid synthesis compartmentalization among cytosol and plastid (Bohlmann et al., 1998b; Chen et al., 2011; Tholl and Lee, 2011), reflecting the circumstance that monoterpene and diterpene synthases harboring a chloroplast-targeting peptide are functionally active in plastids and sesquiterpene synthases lacking the target peptide are active in cytosol. However, recent findings of the capacity for multi-substrate use of several mono, sesqui-, and, diterpene synthases suggest that when substrate becomes available, several cytosolic “sesquiterpene” synthases could also operate as monoterpene synthases, and analogously, multi-substrate “monoterpene” and “diterpene” synthases could operate as sesquiterpene synthases in plastids (denoted by thin arrows). In addition, terpenoid synthesis can also potentially occur in mitochondria (Nagegowda, 2010; Tholl and Lee, 2011; Dong et al., 2016). For instance, targeting linalool/(E)-nerolidol synthase (FaNES1) from Fragaria ananassa (Table 1 for protein specifics) to the mitochondria led to the production of (E)-nerolidol and homoterpene 4,8-dimethyl nona-1,3,7-triene (DMNT) in transgenic Arabidopsis thaliana plants (Kappers et al., 2005). DMADP, dimethylallyl diphosphate (C5); MEP pathway, 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway; IDP, isopentenyl diphosphate (C5); FDP, farnesyl diphosphate (C15); GDP, geranyl diphosphate (C10); GGDP, geranylgeranyl diphosphate (C20); NDP, neryl diphosphate (C10).

Mentions: The biological significance of the finding of multi-substrate use has been debated as according to the current consensus, hemiterpene, monoterpene, and diterpene syntheses are confined to plastids and rely on substrates provided by the MEP pathway, while sesquiterpene synthesis is confined to cytosol and relies on substrates provided by the MVA pathway (Figure 1; Dudareva et al., 2004, 2006; Keeling et al., 2008). However, there has been significant progress in understanding the subcellular distribution of substrates with differing chain length and cross-talk between the two pathways for substrate formation (Gutensohn et al., 2013; Rasulov et al., 2015; Dong et al., 2016). Since in plants both pathways (MEP and MVA) synthesize the same substrates, DMADP and IDP, there has been a long-standing enigma as to whether the two pathways can exchange metabolites (Rodriguez-Concepcion and Boronat, 2002). A certain exchange of IDP between cytosolic and plastidic compartments has been considered as the most likely point of convergence of the two pathways (Schwender et al., 2001; Bick and Lange, 2003). Although the overall intercompartmental exchange of terpene substrates from one compartment to pathway flux in the other subcellular compartment is minor under non-stressed conditions, the importance of cross-talk among the pathways might increase under stress conditions that particularly suppress terpene synthesis in one pathway or under certain developmental stages (Dudareva et al., 2005; Maya et al., 2013; Rasulov et al., 2015). Furthermore, substrate exchange at the level of larger isoprenoids such as GDP has been also shown to be possible (Bick and Lange, 2003; Dong et al., 2016). In fact, several recent reports demonstrate that monoterpenes can be synthesized by multi-substrate sesquiterpene synthases in the cytosol (Davidovich-Rikanati et al., 2008; Gutensohn et al., 2013). Such a multi-substrate use capacity can provide an alternative means for regulation of mono- and sesquiterpene production through modification of cytosolic pool sizes of different substrates. On the other hand there is evidence of sesquiterpene production in plastids (Van Schie et al., 2007; Nagegowda, 2010). Furthermore, mitochondria could potentially contribute to both mono- and sesquiterpene synthesis (Figure 1, Tholl and Lee, 2011; Dong et al., 2016).


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

Pazouki L, Niinemets Ü - Front Plant Sci (2016)

Terpene biosynthetic pathways and their subcellular compartmentalization in plants. Thick arrows denote the classical understanding of terpenoid synthesis compartmentalization among cytosol and plastid (Bohlmann et al., 1998b; Chen et al., 2011; Tholl and Lee, 2011), reflecting the circumstance that monoterpene and diterpene synthases harboring a chloroplast-targeting peptide are functionally active in plastids and sesquiterpene synthases lacking the target peptide are active in cytosol. However, recent findings of the capacity for multi-substrate use of several mono, sesqui-, and, diterpene synthases suggest that when substrate becomes available, several cytosolic “sesquiterpene” synthases could also operate as monoterpene synthases, and analogously, multi-substrate “monoterpene” and “diterpene” synthases could operate as sesquiterpene synthases in plastids (denoted by thin arrows). In addition, terpenoid synthesis can also potentially occur in mitochondria (Nagegowda, 2010; Tholl and Lee, 2011; Dong et al., 2016). For instance, targeting linalool/(E)-nerolidol synthase (FaNES1) from Fragaria ananassa (Table 1 for protein specifics) to the mitochondria led to the production of (E)-nerolidol and homoterpene 4,8-dimethyl nona-1,3,7-triene (DMNT) in transgenic Arabidopsis thaliana plants (Kappers et al., 2005). DMADP, dimethylallyl diphosphate (C5); MEP pathway, 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway; IDP, isopentenyl diphosphate (C5); FDP, farnesyl diphosphate (C15); GDP, geranyl diphosphate (C10); GGDP, geranylgeranyl diphosphate (C20); NDP, neryl diphosphate (C10).
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Figure 1: Terpene biosynthetic pathways and their subcellular compartmentalization in plants. Thick arrows denote the classical understanding of terpenoid synthesis compartmentalization among cytosol and plastid (Bohlmann et al., 1998b; Chen et al., 2011; Tholl and Lee, 2011), reflecting the circumstance that monoterpene and diterpene synthases harboring a chloroplast-targeting peptide are functionally active in plastids and sesquiterpene synthases lacking the target peptide are active in cytosol. However, recent findings of the capacity for multi-substrate use of several mono, sesqui-, and, diterpene synthases suggest that when substrate becomes available, several cytosolic “sesquiterpene” synthases could also operate as monoterpene synthases, and analogously, multi-substrate “monoterpene” and “diterpene” synthases could operate as sesquiterpene synthases in plastids (denoted by thin arrows). In addition, terpenoid synthesis can also potentially occur in mitochondria (Nagegowda, 2010; Tholl and Lee, 2011; Dong et al., 2016). For instance, targeting linalool/(E)-nerolidol synthase (FaNES1) from Fragaria ananassa (Table 1 for protein specifics) to the mitochondria led to the production of (E)-nerolidol and homoterpene 4,8-dimethyl nona-1,3,7-triene (DMNT) in transgenic Arabidopsis thaliana plants (Kappers et al., 2005). DMADP, dimethylallyl diphosphate (C5); MEP pathway, 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway; IDP, isopentenyl diphosphate (C5); FDP, farnesyl diphosphate (C15); GDP, geranyl diphosphate (C10); GGDP, geranylgeranyl diphosphate (C20); NDP, neryl diphosphate (C10).
Mentions: The biological significance of the finding of multi-substrate use has been debated as according to the current consensus, hemiterpene, monoterpene, and diterpene syntheses are confined to plastids and rely on substrates provided by the MEP pathway, while sesquiterpene synthesis is confined to cytosol and relies on substrates provided by the MVA pathway (Figure 1; Dudareva et al., 2004, 2006; Keeling et al., 2008). However, there has been significant progress in understanding the subcellular distribution of substrates with differing chain length and cross-talk between the two pathways for substrate formation (Gutensohn et al., 2013; Rasulov et al., 2015; Dong et al., 2016). Since in plants both pathways (MEP and MVA) synthesize the same substrates, DMADP and IDP, there has been a long-standing enigma as to whether the two pathways can exchange metabolites (Rodriguez-Concepcion and Boronat, 2002). A certain exchange of IDP between cytosolic and plastidic compartments has been considered as the most likely point of convergence of the two pathways (Schwender et al., 2001; Bick and Lange, 2003). Although the overall intercompartmental exchange of terpene substrates from one compartment to pathway flux in the other subcellular compartment is minor under non-stressed conditions, the importance of cross-talk among the pathways might increase under stress conditions that particularly suppress terpene synthesis in one pathway or under certain developmental stages (Dudareva et al., 2005; Maya et al., 2013; Rasulov et al., 2015). Furthermore, substrate exchange at the level of larger isoprenoids such as GDP has been also shown to be possible (Bick and Lange, 2003; Dong et al., 2016). In fact, several recent reports demonstrate that monoterpenes can be synthesized by multi-substrate sesquiterpene synthases in the cytosol (Davidovich-Rikanati et al., 2008; Gutensohn et al., 2013). Such a multi-substrate use capacity can provide an alternative means for regulation of mono- and sesquiterpene production through modification of cytosolic pool sizes of different substrates. On the other hand there is evidence of sesquiterpene production in plastids (Van Schie et al., 2007; Nagegowda, 2010). Furthermore, mitochondria could potentially contribute to both mono- and sesquiterpene synthesis (Figure 1, Tholl and Lee, 2011; Dong et al., 2016).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Physiology, Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences Tartu, Estonia.

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.

No MeSH data available.


Related in: MedlinePlus