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A Novel Class of Plant Type III Polyketide Synthase Involved in Orsellinic Acid Biosynthesis from Rhododendron dauricum

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ABSTRACT

Rhododendron dauricum L. produces daurichromenic acid, the anti-HIV meroterpenoid consisting of sesquiterpene and orsellinic acid (OSA) moieties. To characterize the enzyme responsible for OSA biosynthesis, a cDNA encoding a novel polyketide synthase (PKS), orcinol synthase (ORS), was cloned from young leaves of R. dauricum. The primary structure of ORS shared relatively low identities to those of PKSs from other plants, and the active site of ORS had a unique amino acid composition. The bacterially expressed, recombinant ORS accepted acetyl-CoA as the preferable starter substrate, and produced orcinol as the major reaction product, along with four minor products including OSA. The ORS identified in this study is the first plant PKS that generates acetate-derived aromatic tetraketides, such as orcinol and OSA. Interestingly, OSA production was clearly enhanced in the presence of Cannabis sativa olivetolic acid cyclase, suggesting that the ORS is involved in OSA biosynthesis together with an unidentified cyclase in R. dauricum.

No MeSH data available.


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The proposed biosynthetic pathway of DCA (A) and the established biosynthetic route to major cannabinoids (B). Both pathways consist of (1) polyketide formation, (2) prenylation, and (3) cyclization steps. The polyketide formation steps of each pathway are enclosed in dashed squares. aIn the absence of OAC, the pentyl tetra-β-ketide intermediate is spontaneously cyclized to olivetol via decarboxylative aldol condensation. Abbreviations used are: OAC, olivetolic acid cyclase; TKS, tetraketide synthase.
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Figure 1: The proposed biosynthetic pathway of DCA (A) and the established biosynthetic route to major cannabinoids (B). Both pathways consist of (1) polyketide formation, (2) prenylation, and (3) cyclization steps. The polyketide formation steps of each pathway are enclosed in dashed squares. aIn the absence of OAC, the pentyl tetra-β-ketide intermediate is spontaneously cyclized to olivetol via decarboxylative aldol condensation. Abbreviations used are: OAC, olivetolic acid cyclase; TKS, tetraketide synthase.

Mentions: Rhododendron dauricum L. (Ericaceae) produces daurichromenic acid (DCA), the unique meroterpenoid composed of sesquiterpene and orsellinic acid (OSA) moieties (Kashiwada et al., 2001) (Figure 1A). DCA has attracted considerable attention because it displays various interesting pharmacological activities, including a potent anti-HIV effect (Iwata et al., 2004; Hashimoto et al., 2005; Tokuyama et al., 2007; Iwata and Kitanaka, 2010; Lee, 2010). Thus, chemical syntheses of DCA have been extensively studied over the past few years (Liu and Woggon, 2010; Bukhari et al., 2015; Luo et al., 2015; Elliott et al., 2016).


A Novel Class of Plant Type III Polyketide Synthase Involved in Orsellinic Acid Biosynthesis from Rhododendron dauricum
The proposed biosynthetic pathway of DCA (A) and the established biosynthetic route to major cannabinoids (B). Both pathways consist of (1) polyketide formation, (2) prenylation, and (3) cyclization steps. The polyketide formation steps of each pathway are enclosed in dashed squares. aIn the absence of OAC, the pentyl tetra-β-ketide intermediate is spontaneously cyclized to olivetol via decarboxylative aldol condensation. Abbreviations used are: OAC, olivetolic acid cyclase; TKS, tetraketide synthase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037138&req=5

Figure 1: The proposed biosynthetic pathway of DCA (A) and the established biosynthetic route to major cannabinoids (B). Both pathways consist of (1) polyketide formation, (2) prenylation, and (3) cyclization steps. The polyketide formation steps of each pathway are enclosed in dashed squares. aIn the absence of OAC, the pentyl tetra-β-ketide intermediate is spontaneously cyclized to olivetol via decarboxylative aldol condensation. Abbreviations used are: OAC, olivetolic acid cyclase; TKS, tetraketide synthase.
Mentions: Rhododendron dauricum L. (Ericaceae) produces daurichromenic acid (DCA), the unique meroterpenoid composed of sesquiterpene and orsellinic acid (OSA) moieties (Kashiwada et al., 2001) (Figure 1A). DCA has attracted considerable attention because it displays various interesting pharmacological activities, including a potent anti-HIV effect (Iwata et al., 2004; Hashimoto et al., 2005; Tokuyama et al., 2007; Iwata and Kitanaka, 2010; Lee, 2010). Thus, chemical syntheses of DCA have been extensively studied over the past few years (Liu and Woggon, 2010; Bukhari et al., 2015; Luo et al., 2015; Elliott et al., 2016).

View Article: PubMed Central - PubMed

ABSTRACT

Rhododendron dauricum L. produces daurichromenic acid, the anti-HIV meroterpenoid consisting of sesquiterpene and orsellinic acid (OSA) moieties. To characterize the enzyme responsible for OSA biosynthesis, a cDNA encoding a novel polyketide synthase (PKS), orcinol synthase (ORS), was cloned from young leaves of R. dauricum. The primary structure of ORS shared relatively low identities to those of PKSs from other plants, and the active site of ORS had a unique amino acid composition. The bacterially expressed, recombinant ORS accepted acetyl-CoA as the preferable starter substrate, and produced orcinol as the major reaction product, along with four minor products including OSA. The ORS identified in this study is the first plant PKS that generates acetate-derived aromatic tetraketides, such as orcinol and OSA. Interestingly, OSA production was clearly enhanced in the presence of Cannabis sativa olivetolic acid cyclase, suggesting that the ORS is involved in OSA biosynthesis together with an unidentified cyclase in R. dauricum.

No MeSH data available.


Related in: MedlinePlus