Peptide name : Copal-8-ol diphosphate hydratase TPSSA3

Source/Organism : Clary sage

Linear/Cyclic : Linear

Chirality : Not found

Peptide length: 785

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : IC50 : 7.10 μM

Cell line : SiHa

Cancer type : Metastatic breast cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 89773.1527 Dalton

Aliphatic index : 0.921

Instability index : 45.8574

Hydrophobicity (GRAVY) : -0.280

Isoelectric point : 5.5386

Charge (pH 7) : -22.3055

Aromaticity : 0.099

Molar extinction coefficient (cysteine, cystine): (125710, 126460)

Hydrophobic/hydrophilic ratio : 0.91463414

hydrophobic moment : 0.0024

Missing amino acid : None

Most occurring amino acid : L

Most occurring amino acid frequency : 93

Least occurring amino acid : C

Least occurring amino acid frequency : 12

Secondary structure fraction (Helix, Turn, Sheet): (0.3, 0.2, 0.3)

SMILES Notation: 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1 : Caniard A, et al. Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture. BMC Plant Biol. 2012; 12:119. doi: 10.1186/1471-2229-12-119

2 : Schalk M, et al. Toward a biosynthetic route to sclareol and amber odorants. J Am Chem Soc. 2012; 134:18900-3. doi: 10.1021/ja307404u

3 : Liu Y, et al. Non-volatile natural products in plant glandular trichomes: chemistry, biological activities and biosynthesis. Nat Prod Rep. 2019; 36:626-665. doi: 10.1039/c8np00077h

Paper title : Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture.

Doi : https://doi.org/10.1186/1471-2229-12-119

Abstract : BACKGROUND: Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea) and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species. RESULTS: Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS) enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS) produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP) with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S)-copalyl diphosphate. A class I diTPS (SsSS) then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae). Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants. CONCLUSIONS: SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid specialized metabolite sclareol in a two-step process. They represent two of the first characterized hydroxylating diTPSs in angiosperms and generate the dihydroxylated labdane sclareol without requirement for additional enzymatic oxidation by activities such as cytochrome P450 monoxygenases. Yeast-based production of sclareol by co-expresssion of SsLPPS and SsSS was efficient enough to warrant the development and use of such technology for the biotechnological production of scareol and other oxygenated diterpenes.

Paper title : Toward a biosynthetic route to sclareol and amber odorants.

Doi : https://doi.org/10.1021/ja307404u

Abstract : Ambergris, a waxy substance excreted by the intestinal tract of the sperm whale, has been a highly prized fragrance ingredient for millenia. Because of supply shortage and price inflation, a number of ambergris substitutes have been developed by the fragrance industry. One of the key olfactory components and most appreciated substitutes of ambergris, Ambrox is produced industrially by semisynthesis from sclareol, a diterpene-diol isolated from Clary sage. In the present study, we report the cloning and functional characterization of the enzymes responsible for the biosynthesis of sclareol. Furthermore, we reconstructed the sclareol biosynthetic pathway in genetically engineered Escherichia coli and reached sclareol titers of ~1.5 g/L in high-cell-density fermentation. Our work provides a basis for the development of an alternative, sustainable, and cost-efficient route to sclareol and other diterpene analogues.

Paper title : Non-volatile natural products in plant glandular trichomes: chemistry, biological activities and biosynthesis.

Doi : https://doi.org/10.1039/c8np00077h

Abstract : Covering: 1960s to end of August 2018 Plant glandular trichomes (GTs) are adaptive structures that are well known as "phytochemical factories" due to their impressive capacity to biosynthesize and store large quantities of specialized natural products. The natural products in GTs are chemically diverse and mostly function as defense chemicals, therefore GTs are frequently regarded as "the first defense line" of plants against biotic and abiotic stresses. More importantly, many GT natural products are commercially desirable, thanks to their significant biological activities, thus attracting extensive interest in their biosynthesis. Consequently, it is well known that plant GTs are not only important reservoirs of biologically active natural products but are also a valuable bank of novel biosynthetic genes and enzymes. The non-volatile or oxygenated natural products in plant GTs, which need longer biosynthetic pathways and more energy from the plants, are of particular interest due to their more extensive biological activities and high commercial value. This review mainly focuses on these non-volatile natural products in plant GTs, including their chemistry, biological activities and biosynthesis. The methods employed for investigating natural products and their biosynthesis in plant GTs are also comprehensively discussed.