The Gymnosperm Cytochrome P450 CYP750B1 Catalyzes Stereospecific Monoterpene Hydroxylation of (+)-Sabinene in Thujone Biosynthesis in Western Redcedar

Gesell, Andreas; Blaukopf, Markus; Madilao, Lina; Yuen, Macaire Man Saint; Withers, Stephen G.; Mattsson, Jim; Russell, John H.; Bohlmann, Jörg

doi:10.1104/pp.15.00315

Cited by 37 publications

(29 citation statements)

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“…In the CYP71 clan, 8 CYP76AA and 18 CYP750 gymnosperm-specific members were identified among the 118 full-length CYP450s. Previous research revealed that the gymnosperms CYP76AA25 and CYP750B1 can catalyze the hydroxylation of sabinene to trans-sabin-3-ol from Thuja plicata (Bohlmann et al, 2015 ). The CYP85 clan, which includes many gymnosperm CYP450s, is involved in the biosynthesis of plant metabolites (Hamberger and Bohlmann, 2006 ; Zerbe et al, 2013 ): the CYP720B is a conifer-specific subfamily with four members in T. chinensis , and the CYP720B4 has been characterized in the biosynthesis of dehydroabietic acid, an ingredient related to the insect resistance of Picea sitchensis (Hamberger et al, 2011 ); the CYP716B is a gymnosperm-specific subfamily, with three members found in T. chinensis , and the sole functionally determined CYP716B gene is a taxoid 9α-hydroxylase in Ginkgo biloba (Zhang et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Assembly and Systematic Identification of Novel Cytochrome P450s in Taxus chinensis

et al. 2017

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Taxus spp. is a highly valuable medicinal plant with multiple pharmacological effects on various cancers. Cytochrome P450s (CYP450s) play important roles in the biosynthesis of active compounds in Taxus spp., such as the famous diterpenoid, Taxol. However, some specific CYP450 enzymes involved in the biosynthesis of Taxol remain unknown, and the systematic identification of CYP450s in Taxus has not been reported. In this study, 118 full-length and 175 partial CYP450 genes were identified in Taxus chinensis transcriptomes. The 118 full-length genes were divided into 8 clans and 29 families. The CYP71 clan included all A-type genes (52) belonging to 11 families. The other seven clans possessed 18 families containing 66 non-A-type genes. Two new gymnosperm-specific families were discovered, and were named CYP864 and CYP947 respectively. Protein sequence alignments revealed that all of the T. chinensis CYP450s hold distinct conserved domains. The expression patterns of all 118 CYP450 genes during the long-time subculture and MeJA elicitation were analyzed. Additionally, the expression levels of 15 novel CYP725 genes in different Taxus species were explored. Considering all the evidence, 6 CYP725s were identified to be candidates for Taxol biosynthesis. The cis-regulatory elements involved in the transcriptional regulation were also identified in the promoter regions of CYP725s. This study presents a comprehensive overview of the CYP450 gene family in T. chinensis and can provide important insights into the functional gene studies of Taxol biosynthesis.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Assembly and Systematic Identification of Novel Cytochrome P450s in Taxus chinensis

et al. 2017

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“…The most closely related and functionally defined P450s are L. japonicus LjCYP736A2 (cyanogenic glucoside metabolism; Takos et al, 2011) and S. aucuparia SoCYP736A107 (noraucuparin formation in biphenyl phytoalexin biosynthesis; Sircar et al, 2015). The CYP750B1 sabinene hydroxylase of the gymnosperm Thuja plicata appears to be the most closely related P450, with a known function in terpenoid oxidation (Gesell et al, 2015). Individually scaled TIC Figure S4).…”

Section: Phylogenetic Relationships For Sacyp736a167mentioning

confidence: 99%

Heartwood‐specific transcriptome and metabolite signatures of tropical sandalwood (Santalum album) reveal the final step of (Z)‐santalol fragrance biosynthesis

et al. 2016

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SUMMARYTropical sandalwood (Santalum album) produces one of the world's most highly prized fragrances, which is extracted from mature heartwood. However, in some places such as southern India, natural populations of this slow-growing tree are threatened by over-exploitation. Sandalwood oil contains four major and fragrance-defining sesquiterpenols:The first committed step in their biosynthesis is catalyzed by a multi-product santalene/bergamotene synthase. Sandalwood cytochromes P450 of the CYP76F sub-family were recently shown to hydroxylate santalenes and bergamotene; however, these enzymes produced mostly (E)-santalols and (E)-a-exo-bergamotol. We hypothesized that different santalene/bergamotene hydroxylases evolved in S. album to stereo-selectively produce (E)-or (Z)-sesquiterpenols, and that genes encoding (Z)-specific P450s contribute to sandalwood oil formation if co-expressed in the heartwood with upstream genes of sesquiterpene biosynthesis. This hypothesis was validated by the discovery of a heartwood-specific transcriptome signature for sesquiterpenoid biosynthesis, including highly expressed SaCYP736A167 transcripts. We characterized SaCYP736A167 as a multi-substrate P450, which stereo-selectively produces (Z)-a-santalol, (Z)-b-santalol, (Z)-epi-b-santalol and (Z)-a-exo-bergamotol, matching authentic sandalwood oil. This work completes the discovery of the biosynthetic enzymes of key components of sandalwood fragrance, and highlights the evolutionary diversification of stereo-selective P450s in sesquiterpenoid biosynthesis. Bioengineering of microbial systems using SaCYP736A167, combined with santalene/bergamotene synthase, has potential for development of alternative industrial production systems for sandalwood oil fragrances.

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“…The next biosynthetic step leads from sabinene to either (? )-trans-sabinol in the case of gymnosperm T. plicata (Gesell et al 2015) or (-) cis-sabinol in the angiosperm S. officinalis (Karp and Croteau 1982). Gesell et al (2015) identified CYP750B1 and CYP76AA25 as the enzymes catalyzing the hydroxylation of (?…”

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confidence: 99%

“…)-sabinene to trans-sabin-3-ol. The role of the first enzyme is essential and it seems to be strongly substrate specific, while the CYP76AA25 has a broader substrate spectrum and its transcript profiles were not well correlated with thujone accumulation (Gesell et al 2015). Earlier, Karp and Croteau (1982) suggested (-)-cis-sabinol to be the intermediary of the same pathway in sage; however, it is not known if the synthesis in Artemisia and other species is going on through trans-or cissabinol.…”

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confidence: 99%

Thujone, a widely debated volatile compound: What do we know about it?

Németh

Nguyen

2020

Phytochem Rev

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Thujone is a volatile monoterpene ketone of plant origin which is produced by several plants that are frequently used for flavoring foods and beverages. The use of thujone and thujone-containing plant parts for human consumption is currently regulated by the European Parliament and Council and the European Medicines Agency. The best known neurotoxic effects are connected to the GABA-gated chloride channel, where a-thujone is a modulator roughly two to three times as potent as the b isomer. Based primarily on in vitro experiments, genotoxicity and carcinogenic properties of thujones have also been detected in parallel with antimutagenic and immune-modulatory effects. Some of the controversial effects seem to be strongly dose-dependent. Data on antidiabetic and antimicrobial activities of thujones may show new ways to use them. This review also describes the main steps of the biosynthetic route of thujones and their occurrence in the plant kingdom. The accumulation of these compounds seems to be more abundant in some plant families (e.g. Asteraceae or Cupressaceae) than in others. Four species (Artemisia absinthium, Salvia

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The Gymnosperm Cytochrome P450 CYP750B1 Catalyzes Stereospecific Monoterpene Hydroxylation of (+)-Sabinene in Thujone Biosynthesis in Western Redcedar

Cited by 37 publications

References 51 publications

Transcriptome Assembly and Systematic Identification of Novel Cytochrome P450s in Taxus chinensis

Transcriptome Assembly and Systematic Identification of Novel Cytochrome P450s in Taxus chinensis

Heartwood‐specific transcriptome and metabolite signatures of tropical sandalwood (Santalum album) reveal the final step of (Z)‐santalol fragrance biosynthesis

Thujone, a widely debated volatile compound: What do we know about it?

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