Enhanced structural diversity in terpenoid biosynthesis: enzymes, substrates and cofactors

Vattekkatte, Abith; Garms, Stefan; Brandt, Wolfgang; Boland, Wilhelm

doi:10.1039/c7ob02040f

Cited by 45 publications

(53 citation statements)

References 125 publications

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“…Natural class I terpene synthases precisely pre-orient their acyclic diphosphate substrates in their active site pockets in a reaction-ready conformation. Then, the complex reaction cascade is initiated by cleaving off the diphosphate group from the pre-oriented substrate molecule, a pH-dependent [4] process that requires divalent metal ions as cofactor [28,29]. It has been shown that this ionization step of the allylic diphosphate is the rate-limiting step in a class I terpene synthetase catalysis [30].…”

Section: Protonation-dependent Diphosphate Cleavagementioning

confidence: 99%

“…We also introduce a graph database to integrate the simulation results with experimental biological evidence for the selected predicted sesquiterpenes biosynthesis.Processes 2019, 7, 240 2 of 18 "biogenetic isoprene rule" according to which terpenes are the result of concatenating isoprene units in a "head-to-tail" fashion to form chains, from which then rings are formed. Prenyltransferases condense IPP and DMAPP to geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP) as the entry points to the world of monoterpenes (C 10 ), sesquiterpenes (C 15 ), and diterpenes(C 20 ) [4]. FPP and GGPP can then be condensed further to form squalene (C 30 ) and even largermolecules [5].These intermediates are substrates for a class of enzymes known collectively as terpene synthases (TPSs) to produce a wide variety of compounds.…”

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confidence: 99%

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Exploring Plant Sesquiterpene Diversity by Generating Chemical Networks

et al. 2019

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Plants produce a diverse portfolio of sesquiterpenes that are important in their response to herbivores and the interaction with other plants. Their biosynthesis from farnesyl diphosphate depends on the sesquiterpene synthases that admit different cyclizations and rearrangements to yield a blend of sesquiterpenes. Here, we investigate to what extent sesquiterpene biosynthesis metabolic pathways can be reconstructed just from the knowledge of the final product and the reaction mechanisms catalyzed by sesquiterpene synthases. We use the software package MedØlDatschgerl (MØD) to generate chemical networks and to elucidate pathways contained in them. As examples, we successfully consider the reachability of the important plant sesquiterpenes β -caryophyllene, α -humulene, and β -farnesene. We also introduce a graph database to integrate the simulation results with experimental biological evidence for the selected predicted sesquiterpenes biosynthesis.

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Section: Protonation-dependent Diphosphate Cleavagementioning

confidence: 99%

mentioning

confidence: 99%

Exploring Plant Sesquiterpene Diversity by Generating Chemical Networks

et al. 2019

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“…Natural class I terpene synthetases precisely pre-orient their acyclic diphosphate substrates in their active-site pockets in a reaction ready conformation. The complex reaction cascade is than initiated by cleaving off the diphosphate group from the pre-oriented substrate molecule, a pH-dependent [4] process that requires divalent metal ions as co-factor [25,26]. It has been shown, that this ionization step of the allylic diphosphate is the rate-limiting step in class I terpene synthetase catalysis [27].…”

Section: Protonation-dependent Diphosphate Cleavagementioning

confidence: 99%

“…Leopold Ružička [3] formulated the "biogenetic isoprene rule" according to which terpenes are the result of concatenating isoprene units in a "head-to-tail" fashion to form chains, from which then rings are formed. Prenyltransferases condense IPP and DMAPP to geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP) as the entry points to the world of monoterpenes (C 10 ), sesquiterpenes (C 15 ), and diterpenes (C 20 ) [4]. FPP and GGPP can then be condensed further to form squalene (C 30 ) and even larger molecules [5].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, there are only four dominating types of cyclization reactions initiating the complex reaction cascade: C 1 − C 10 , C 1 − C 11 , C 1 − C 6 , and C 1 − C 7 [14]. Even though the electrophilic chemical reaction mechanisms [11] primarily determine the diversity of the products, many other factors influence multiproduct sesquiterpene enzymes and their cyclization cascades, such as pH, the metal cofactor [4], evolutionary forces for the functional divergence [15], and plant-plant interactions [16].…”

Section: Introductionmentioning

confidence: 99%

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Exploring Plant Sesquiterpene Diversity by Generating Chemical Networks

Silva¹,

Andersen

Holanda³

et al. 2019

Preprint

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Plants produce a diverse portfolio of sesquiterpenes that are important in their response to herbivores and the interaction with other plants. Their biosynthesis from farnesyl diphosphate depends on the sesquiterpene synthases. Here, we investigate to what extent metabolic pathways can be reconstructed just from knowledge of the final product and the reaction mechanisms catalyzed by sesquiterpene synthases. We use the software package MedØlDatschgerl (MØD) to generate chemical networks and elucidate pathways contained in them. As examples, we successfully consider the reachability of the important plant sesquiterpenes β-caryophyllene, α-humulene, and β-farnesene. We also introduce a graph database to integrate simulation results with experimental biological evidence for selected predicted sesquiterpenes biosynthesis.

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Biokatalytische Entstehung von Sesquiterpenoiden

Püth,

Berger,

Krings

et al. 2024

Lebensmittelchemie

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Aromastoffe spielen eine Schlüsselrolle in der Lebensmittelindustrie und bei der Kaufentscheidung der Verbraucher. Dabei achten Kunden verstärkt auf die Natürlichkeit der Produkte und nachhaltige Herstellungsverfahren. Um diesen Vorgaben nachzukommen, rücken höhere Pilze als Produzenten von natürlichen Aromastoffen sowie als Quelle für lebensmitteltechnologisch relevante Enzyme zur Herstellung und Qualitätsverbesserung von Lebensmitteln in den Fokus.Im Rahmen der vorliegenden Arbeit wurde der Basidiomycet Cerrena unicolor (Cun) als Sesquiterpenproduzent untersucht. Im Genom des Pilzes konnten mit Hilfe von Sequenzvergleichen 14 Sesquiterpensynthasen (STS) identifiziert werden. Zehn von ihnen wurden anschließend erfolgreich heterolog in Escherichia coli exprimiert, die Enzyme produziert und funktionell charakterisiert. Mittels tryptischem Verdau und anschließendem peptide mass fingerprinting konnten die vorhergesagten Proteinsequenzen bestätigt werden. Die Sequenzvergleiche zeigten STS‐typische konservierte Motive sowie möglicherweise für Cun spezifische Homologien. Für die Untersuchung der Metallionenabhängigkeit wurden zwei STS aus Cun gewählt, die sich sowohl in der Anzahl der Produkte, als auch den produzierten Sesquiterpenen selbst unterschieden. Setzte man andere bivalente Metallionen als Mg2+ für die Zyklisierungsreaktion ein, zeigte sich, dass die ausgewählte Multiprodukt‐Cyclase promiskuitiver als die Cyclase mit nur einem Sesquiterpen als Produkt reagierte.Weiterhin konnte gezeigt werden, dass agro‐industrielle Nebenströme für die Kultivierung von Cun verwendet werden können und diese Einfluss auf die Sesquiterpenbiosynthese hatten. Eher kohlenhydratreiche Nebenströme wie Kartoffelstärke oder Weizenkleie hatten keinen positiven Einfluss auf die Produktausbeute. Für den lipidhaltigen Rapspresskuchen konnte jedoch eine deutliche Erhöhung der Produktausbeute nachgewiesen werden. Die Hypothese, dass durch β‐Oxidation der Lipide ein Überfluss an Acetyl‐CoA die Sesquiterpenproduktion boostet, konnte mittels 13C‐markiertem Acetat als Medienzusatz experimentell bestätigt werden.

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Enhanced structural diversity in terpenoid biosynthesis: enzymes, substrates and cofactors

Cited by 45 publications

References 125 publications

Exploring Plant Sesquiterpene Diversity by Generating Chemical Networks

Exploring Plant Sesquiterpene Diversity by Generating Chemical Networks

Exploring Plant Sesquiterpene Diversity by Generating Chemical Networks

Biokatalytische Entstehung von Sesquiterpenoiden

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