The biosynthesis of steroids and triterpenoids

Brown, Geoffrey D.

doi:10.1039/a815653y

Cited by 85 publications

(52 citation statements)

References 1,309 publications

(1,214 reference statements)

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“…6; Brown, 1998). The presence of multiple fpps genes in A. tridentata, each with about 80% identity, suggested that the encoded isozymes function specifically.…”

Section: Discussionmentioning

confidence: 99%

Silencing Geranylgeranyl Diphosphate Synthase inNicotiana attenuataDramatically Impairs Resistance to Tobacco Hornworm

et al. 2007

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In bioassays with artificial diets, the 17-hydroxygeranyllinalool diterpenoid glycosides (HGL-DTGs) of Nicotiana attenuata function as antifeedants for the plant's adapted herbivore, tobacco hornworm (Manduca sexta). To determine whether HGLDTGs have a defensive function in planta, we suppressed HGL-DTG production by silencing the source of the geranylgeranyl diphosphates (GGPPs) required for geranyllinalool biosynthesis, a key intermediate. We used virus-induced gene silencing to suppress transcript levels of GGPP synthase gene (Naggpps) and farnesyl diphosphate (FPP) synthase gene (Nafpps), northern blotting and real-time polymerase chain reaction to quantify transcript accumulations, and radio gas chromatography to analyze prenyltransferase specificity. Silencing Nafpps had no effect on the accumulation of HGL-DTGs but decreased leaf steroid content, demonstrating that DTG-synthesizing enzymes do not use GGPP derived from FPP and confirming FPP's role as a steroid precursor. Unlike plants silenced in the phytoene desaturase gene (Napds), which rapidly bleached, Naggppssilenced plants had reduced HGL-DTG but not carotenoids or chlorophyll contents, demonstrating that Naggpps supplies substrates for GGPP biosynthesis for HGL-DTGs, but not for phytoene or phytol. Expression of Naggpps in Escherichia coli revealed that the recombinant protein catalyzes the GGPP synthesis from isopentenyl diphosphate and dimethylallyl diphosphate. When fed on silenced plants, hornworm larvae gained up to 3 times more mass than those that fed on empty vector control plants or plants silenced in Nafpps, the trypsin protease inhibitor gene, or the putrescine N-methyltransferase gene. We conclude that HGL-DTGs or other minor undetected diterpenoids derived from GGPP function as direct defenses for N. attenuata and are more potent than nicotine or trypsin protease inhibitors against attack by hornworm larvae.

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“…6; Brown, 1998). The presence of multiple fpps genes in A. tridentata, each with about 80% identity, suggested that the encoded isozymes function specifically.…”

Section: Discussionmentioning

confidence: 99%

Silencing Geranylgeranyl Diphosphate Synthase inNicotiana attenuataDramatically Impairs Resistance to Tobacco Hornworm

et al. 2007

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“…However, three putative precursors have been postulated for IPP formation i.e. mevalonate (Brown 1998), deoxyxylulose (Rohmer et al 1993) and in some plants, amino acids (Suga et al 1980, Koops et al 1991. Experiments using labeled compounds revealed that mevalonate is the preferential precursor for sterol (Baisted 1971, Trojanowska et al 2000 and pentacyclic triterpene (van der Heijden et al 1989, Akashi et al 1994 biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

“…Some plants contain large quantities of triterpenes in their latex and resins, and among their physiological functions has been proposed a chemical defense against pathogens and herbivores (Brown 1998). Plant cell cultures can respond to elicitor treatments with the induction of triterpenoid phytoalexins (van der Heijden et al 1989), while this pathway could be inhibited using specific enzyme inhibitors such as terbinafine, which inhibits squalene 2,3-oxide formation (Yates et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of Sterols and Triterpenes in Cell Suspension Cultures of Uncaria tomentosa

Flores-Sánchez

Ortega‐López

Montes-Horcasitas

et al. 2002

Plant and Cell Physiology

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;Pectin administered to Uncaria tomentosa cell suspension cultures, was found to increase the production of triterpene acids (ursolic and oleanolic acid), however, neither growth nor sterol accumulation were affected. Cell cultures showed that pectin treatment caused a rapid threefold increase in the activities of enzymes involved in the biosynthesis of C 5 and C 30 isoprenoid, such as isopentenyl diphosphate isomerase and squalene synthase. The activity of a farnesyl diphosphatase, which could divert the flux of farnesyl diphosphate to farnesol, was two times lower in elicited than in control cells. Elicited cells also transformed more rapidly a higher percentage of [5-3 H]mevalonic acid into triterpene acids. Interestingly, addition of terbinafine, an inhibitor of squalene epoxidase, to elicited cell cultures inhibited sterol accumulation while triterpene production was not inhibited. These results suggest that in U. tomentosa cells, both the previously mentioned enzymes and those involved in squalene 2,3-oxide formation play an important regulatory role in the biosynthesis of sterols and triterpenes.

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“…An exact understanding of fungal ergosterol biosynthesis and metabolism is therefore crucial for the design of novel, more specific and more effective antifungal drugs. Most of the basic research on the biosynthetic pathway leading to ergosterol has focused on the non-pathogenic yeast Saccharomyces cerevisiae [2]. Thus, in 1973, multiple pathways for the ergosterol biosynthesis in yeast were proposed [3].…”

Section: Introductionmentioning

confidence: 99%

Sterols in erg mutants of Phycomyces: metabolic pathways and physiological effects

Barrero¹,

Oltra²,

Robinson³

et al. 2002

Steroids

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Phycomyces is a fungal producer of ␤-carotene and other beneficial metabolites. Several erg mutants of Phycomyces, originally selected to study the effects of membrane alteration on physiological responses, have now been used to gain information about sterol biosynthesis in filamentous fungi. One mutant, H23, and its progeny were found to be blocked at episterol C-5 dehydrogenase and did not produce ergosterol or any other sterol with a conjugated ⌬ 5,7 diene system. This mutant showed abnormal phototropism, which was correlated with the altered sterol composition. Another mutant, H25, seems to be a regulatory mutant. All analyzed mutants synthesized ergosta-7,22,24(28)-trien-3␤-ol, demonstrating for the first time that the sterol C-22 dehydrogenase of Phycomyces is capable of recognizing sterols with a 24(28) unsaturated side chain. New evidence regarding the biogenesis of neoergosterol and phycomysterols, the potential sparking function of cholesterol, as well as the regulation of sterol biosynthesis in this fungus is also reported. Given these results, a pathway for sterol biosynthesis in Phycomyces is proposed.

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The biosynthesis of steroids and triterpenoids

Cited by 85 publications

References 1,309 publications

Silencing Geranylgeranyl Diphosphate Synthase inNicotiana attenuataDramatically Impairs Resistance to Tobacco Hornworm

Silencing Geranylgeranyl Diphosphate Synthase inNicotiana attenuataDramatically Impairs Resistance to Tobacco Hornworm

Biosynthesis of Sterols and Triterpenes in Cell Suspension Cultures of Uncaria tomentosa

Sterols in erg mutants of Phycomyces: metabolic pathways and physiological effects

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