Phytochemistry Reviews (v.15, #5)

Hydroxycinnamoyltransferases are enzymes transferring hydroxycinnamoyl units like cinnamoyl, 4-coumaroyl, caffeoyl, feruloyl and sinapoyl moieties from an activating residue such as coenzyme A or glucose or activated as hydroxycinnamoyl ester (e.g. chlorogenate) to an acceptor molecule, most commonly to an OH or NH2 group as ester or amide. The hydroxycinnamoyl groups play either a “decorating” role or are building blocks of more complex structures. Proteins catalysing hydroxycinnamoyl transfer have been known for many decades and are nowadays investigated on molecular and structural levels. At least four different protein families give rise to enzymes with hydroxycinnamoyltransferase activity: serine carboxypeptidase-like proteins, tyramine hydroxycinnamoyltransferase-like enzymes, BAHD acyltransferases and GDSL-lipase/esterase-like enzymes. Interestingly, the same or very similar products can be formed by enzymes from different enzyme classes and using differently activated hydroxycinnamoyl units. This review will summarise the current literature data on the features of hydroxycinnamoyltransferases from the four different enzyme groups.
Keywords: BAHD acyltransferase; GDSL lipase/esterase-like acyltransferase; Phenolic metabolism; Serine carboxypeptidase-like acyltransferase; THT-like hydroxycinnamoyltransferase

Alkamides are natural products formed by connecting straight-chain, mostly unsaturated, aliphatic acids with various amines by an amide linkage. More than 300 derivatives are known from eight plant families consisting of various combinations of 200 acids with 23 amines. Apart from a few saturated derivatives alkamides with unsaturated acid parts are grouped into compounds with purely olefinic patterns and those with olefinic and acetylenic linkages. Derived from C18 oleic acid the acid parts are modified either by chain elongations to C28 or by oxidative shortenings to C4 acid residues. Substrate and regiospecific desaturases and acetylenases are responsible for their characteristic patterns of unsaturation. Amine parts are derived from various amino acids by decarboxylation. Beside the widespread isobutylamines alkamides with six- and five-membered ring amines and those with phenylalanine derived amines are characteristic for the Asteraceae and Piperaceae while benzylamines are restricted to the Brassicaceae. Within the Asteraceae 2-methylbutylamine distinguishes the tribe Heliantheae from Anthemideae characterized by ring amines. Alkamides with elongated olefinic acid parts are mainly found in Piperaceae and Brassicaceae while acetylenic acid parts are typical for Asteraceae. A wide variety of biological activities ranges from the characteristic pungent/tingling property and high insecticidal toxicity to significant antifungal, antibacterial, antiprotozoal, molluscicidal, cercaricidal, and acaricidal activity. They also act as plant growth-promoting substances. Position and stereochemistry of the double bonds are essential for the different qualities of the pungent taste. Medically alkamides possess anti-inflammatory and analgesic properties and are responsible for immuno-modulatory and cannabinomimetic effects.
Keywords: Structural diversity; Biogenetic trends; Chemotaxonomy; Biological activities; Structure–activity relationships

Phytochemistry and biosynthesis of δ-lactone withanolides by Bing-You Yang; Yong-Gang Xia; Juan Pan; Yan Liu; Qiu-Hong Wang; Hai-Xue Kuang (771-797).
Withanolides are highly oxygenated natural products. These C28 steroids with ergostane-based skeletons functionalized at C-22 and C-26 form six-membered δ-lactone rings. Withanolides containing a δ-lactone side chain often occur in Solanaceae and have a variety of biological activities because of their complicated structures. Characteristic spectroscopic behaviors and biosynthesis of withanolides are conducive to their structural elucidation and “biomimetic synthesis”, respectively. However, the last review to summarize their spectroscopic features and biosynthesis was in 1996. Since then, many withanolides with novel structures have been described by their spectra with biosynthesis investigated with many bioassays. This review surveys δ-lactone withanolides and emphasizes their spectral features, configurations and biosynthetic genes. The period reviewed includes through January 2014. We also include phytochemical species.
Keywords: Biosynthesis; Classification; Phytochemistry; Spectra

Vegetable oils are an essential component of human diet, in terms of their health beneficial roles. Despite their importance, the fatty acid profile of most commonly used edible oil seed crop plants are imbalanced; this skewed ratio of fatty acids in the diet has been shown to be a major reason for the occurrence of cardiovascular and autoimmune diseases. Until recently, it was not possible to exert significant control over the fatty acid composition of vegetable oils derived from different plants. However, the advent of metabolic engineering, knowledge of the genetic networks and regulatory hierarchies in plants have offered novel opportunities to tailor-made the composition of vegetable oils for their optimization in regard to food functionality and dietary requirements. Sesame (Sesamum indicum L.) is one of the ancient oilseed crop in Indian subcontinent but its seed oil is devoid of balanced proportion of ω-6:ω-3 fatty acids. A recent study by our group has shed new lights on metabolic engineering strategies for the purpose of nutritional improvement of sesame seed oil to divert the carbon flux from the production of linoleic acid (C18:2) to α-linolenic acid (C18:3). Apart from that, this review evaluates current understanding of regulation of fatty acid biosynthetic pathways in sesame and attempts to identify the major options of metabolic engineering to produce superior sesame seed oil.
Keywords: 1,2-sn-diacylglycerol acyltransferase; Fatty acid desaturase; Fatty acyl-ACP thioesterase; Sesame seed oil; Stearoyl-acyl-carrier protein Δ9-desaturase

Phytochemistry and pharmacological activities of Vaccaria hispanica (Miller) Rauschert: a review by Guohong Zhou; Liying Tang; Ting Wang; Xidan Zhou; Zhenzhen Kou; Jing Wu; Zhuju Wang (813-827).
Vaccaria hispanica is utilized medicinally both in China and Turkey. Phytochemical screenings demonstrated that the phytochemical diversity of V. hispanica at least includes 63 distinct metabolites, embracing triterpenoid saponins, cyclic peptides, flavonoids and others. The pharmacological studies confirmed that the crude extracts or purified compounds from the plant showed galactopoietic activity, antitumor activity, effect on the blood and vessel, antioxidant activity, ameliorative effect on osteopenia and others. The present paper is aimed to provide a critical analysis of data from scientific evaluations and aimed to find out the linkage of the medicinal uses to the scientific studies. Simultaneously, the possible future direction and perspective for investigations are discussed, as well.
Keywords: Antitumor activity; Cyclic peptide; Vaccaria hispanica ; Galactopoietic activity

Bioactive phytochemicals from shoots and roots of Salvia species by Amir Reza Jassbi; Somayeh Zare; Omidreza Firuzi; Jianbo Xiao (829-867).
The plants of the genus Salvia L. are important medicinal herbs of the Lamiaceae family and some of them such as S. officinalis (sage), S. miltiorrhiza (red sage, Danshen) and S. sclarea (clary sage) have been used as medicinal plants in the folk medicine of several countries. In this review, we discuss the reports that have examined Salvia species with the aim of isolation of pure compounds with different biological activities. The phytochemical analyses of various sage plants have reported 10 monoterpenoids (110), 1 sesquiterpenoid (11), 8 labdane (1320), 15 ent-kaurane (2135), 82 abietane, rearranged abietane and tanshinone (36117), 3 icetexane (118120), 43 clerodane (121163), and 3 pimarane (164166) diterpenoids with cytotoxic and antimicrobial, antiprotozoal, antioxidant, phytotoxic and insecticide effects. The other heavier terpenoids, including 3 sesterterpenes (167169), 10 triterpenoids and β-sitosterol (170180) have been introduced as minor bioactive compounds in the sage plants. Sahandinone (107), 6,7-dehydroroyleanone, 7-α-acetoxyroyleanone (40), and tanshinone like diterpenoids have been isolated from the roots’ extracts of different Salvia species. On the other hand, several radical scavenger phenolic compounds like simple phenolics and caffeic acid derivatives (181201) including rosmarinic acid, flavonoids (202217) as well as phenolic diterpenoids, such as carnosol and carnosic acid have been isolated from the aerial parts of these plants. One pyrrole (218) and 3 antimicrobial oxylipins (219221) are among the other less detected constituents in the members of Salvias. Furthermore, sages also synthesize antifungal, antileishmanial and antimalarial phytochemicals in their roots and shoots, which are reviewed in this paper. We also examine the allelopathic phenomena and the ecologically important phytochemicals identified in different parts of the sage plants. Finally, antifeedant and insecticide phenomena, which are due to the presence of volatile monoterpenes and clerodane diterpenes in these plants, are discussed. Considering the presence of diverse biologically active phytochemicals in the sage plants, they can be suggested as suitable candidates for the formulation of valuable natural medicines.
Keywords: Salvia L.; Cytotoxic activity, antimicrobial and antioxidant activity; Antileishmanial and antimalarial activity; Allelopathic and antifeedant activity

The genus Lindera: a source of structurally diverse molecules having pharmacological significance by Yuan Cao; Bianfei Xuan; Bing Peng; Chun Li; Xingyun Chai; Pengfei Tu (869-906).
Lindera plants not only have good ornamental and economic uses but also have great medicinal and therapeutic values. The genus Lindera consists of approximately 100 species that are widely distributed in tropical and subtropical areas throughout the world. This extensive geographical distribution allows Lindera plants to produce diverse secondary metabolites having novel structures. Phytochemical investigations have shown that Lindera plants produce 341 constituents, including sesquiterpenoids, alkaloids, butanolides, lucidones, flavonoids, and phenylpropanoids. Moreover, some Lindera plants show significant chemotaxonomic reference under family Lauraceae and tribe Litseae. Although Lindera plants have various pharmacological and biological properties, their anticancer, antihypertensive, anti-inflammatory, and analgesic properties have been focused in many studies. Butanolides and lucidones have shown great potential in developing anticancer agents while aporphine alkaloids have shown great potential in developing antiarthritic and antinociceptive agents. However, these compounds need to be assessed further by performing in-depth and systematic research.
Keywords: Lindera ; Lauraceae; Structural diversity; Pharmacological significance; Chemotaxonomy; Review

Khat (Catha edulis) belongs to Celastraceae family which contains 60–70 genera and 850–900 species. It is an indigenous plant to Ethiopia and Yemen as the countries of origin. It is also found in many other east and southern African countries. Khat leaves are chewed by the local people for their stimulant action. The main active ingredient compounds those are responsible for this action is cathinone and a mild stimulant cathine. In addition to these khat contains several phytochemicals such as alkaloids (phenylalkylamines and cathedulins), flavonoids, steroid and triterpenoids, monoterpenes and volatile aromatic compounds, and other miscellaneous compounds like vitamins and amino acids. Hence, this paper presents a comprehensive and unified review of literatures which concerned on the phytochemical composition of khat plant. And it also provides the isolated compounds with their chemical structures.
Keywords: Khat; Catha edulis ; Cathedulins; Cathinone; Cathine; Flavonoids

Biotransformation of Tetrahydrocannabinol by Muhammad T. Akhtar; Khozirah Shaari; Robert Verpoorte (921-934).
Cannabinoids are terpenophenolic compounds consisting of an aromatic polyketide and derived from the geranyl diphosphate C10 terpenoid unit. They are the active constituents in Cannabis sativa and have been utilized in a number of cannabis-based medicines. Biotransformation of cannabinoids is an important field of xenobiochemistry and toxicology and the study of the metabolism of these compounds can lead to the discovery of new compounds, unknown metabolites with unique structures and new therapeutic entities. Different fungi, bacteria, plants and animal cells have been used for the regio- and stereoselective transformation of cannabinoids. All of the above mentioned organisms have distinct enzymes which catalyze the conversion of a specific cannabinoid at different positions and thus provide a variety of derivatives. All organisms are able to transform the alkyl side chain where as mammalians are unique in the formation of the carboxy derivatives. This review article assesses the current knowledge on the biotransformation of tetrahydrocannabinol and with particular focus on ∆9-THC.
Keywords: Metabolism; Mammalian cells; Microorganisms; Plant cells; Tetrahydrocannabinol

Botany, agronomy and biotechnology of Pelargonium used for essential oil production by B. Blerot; S. Baudino; C. Prunier; F. Demarne; B. Toulemonde; J.-C. Caissard (935-960).
Pelargonium is one of the seven genera belonging to the Geraniaceae family, and includes almost 280 species mainly coming from South Africa. Some of these species have a strong rose scent mostly due to geraniol and citronellol. For a long time, hybrids between P. graveolens or P. radens and P. capitatum, have been used for essential oil (EO) production. Nowadays, EOs of Pelargonium species are produced mainly in China and Egypt. Hybrids are male sterile and propagated through cuttings. Their adaptability to different soils and climates (tropical, semi-tropical, mediterranean, or arid) is remarkable, even if cultivation parameters still have to be improved. Methods for genetic transformation of Pelargonium are available and, due to the growing knowledge of biosynthetic pathways and the cloning of terpene synthase genes in angiosperms, new strategies to improve EO yield or to modify EO composition could be imagined. For example, new crossings driven by biotechnological tools, creation of genetically modified Pelargonium with strong promoters upstream of terpene synthase genes, and batch production of Pelargonium terpenoids through recombinant yeasts or bacteria, are very promising approaches to develop EOs.
Keywords: Aromatic plant; Essential oil; Geraniol; ‘Pelargonium rosat’; Terpenes

Elm defence against herbivores and pathogens: morphological, chemical and molecular regulation aspects by Kerstin Büchel; Trevor Fenning; Jonathan Gershenzon; Monika Hilker; Torsten Meiners (961-983).
Elms (Ulmus spp.) have long been appreciated for their environmental tolerance, landscape and ornamental value, and the quality of their wood. Although elm trees are extremely hardy against abiotic stresses such as wind and pollution, they are susceptible to attacks of biotic stressors. Over 100 phytopathogens and invertebrate pests are associated with elms: fungi, bacteria and insects like beetles and moths, and to a lesser extent aphids, mites, viruses and nematodes. While the biology of the pathogen and insect vector of the Dutch elm disease has been intensively studied, less attention has been paid so far to the defence mechanisms of elms to other biotic stressors. This review highlights knowledge of direct and indirect elm defences against biotic stressors focusing on morphological, chemical and gene regulation aspects. First, we report how morphological defence mechanisms via barrier formation and vessel occlusion prevent colonisation and spread of wood- and bark-inhabiting fungi and bacteria. Second, we outline how secondary metabolites such as terpenoids (volatile terpenoids, mansonones and triterpenoids) and phenolics (lignans, coumarins, flavonoids) in leaves and bark are involved in constitutive and induced chemical defence mechanisms of elms. Third, we address knowledge on how the molecular regulation of elm defence is orchestrated through the interaction of a huge variety of stress- and defence-related genes. We conclude by pointing to the gaps of knowledge on the chemical and molecular mechanisms of elm defence against pest insects and diseases. An in-depth understanding of defence mechanisms of elms will support the development of sustainable integrated management of pests and diseases attacking elms.
Keywords: Dutch elm disease; Elm leaf beetle; Chemical response; Morphological defence; Gene regulation; Induced resistance; Terpenoids; Ulmus minor

Forestry residues are a plentiful, low environmental impact feedstock for biofuels and bioproducts. Douglas-fir is the most prevalent tree species in the timberlands of western North America, with approximately 5 million tons of sustainably harvestable forestry residues available each year. These forestry residues are an important potential biomass feedstock containing holocellulose, lignin, protein, ash, and phytochemicals commonly identified as “extractives”. The phytochemical extractive category make up 5–25 % of the dry weight for different tissues of Douglas-fir, but are rarely represented with molecular detail in feedstock models of residues for biofuel or other bioproduct. These extractives contain both primary and secondary metabolites and represent potential revenue sources as side products from processing, but also includes species that are astringent, toxic, endocrine disruptors and/or reactive in similar chemical processes. Within the “extractives” category are phytochemicals such as proanthocyanidins, phlobaphenes, waxes, flavonoids, terpenoids, phytosterols, lignans and many more. This review first identifies phytochemical molecules found in different Douglas-fir tissues, then quantities these by category and individual molecular species, to the extent allowed by the literature. We combine the literature into a quantitative, molecularly detailed, mass conserving model for a particular Douglas-fir forestry residue (“slash”). This model is used in a sulfite/bisulfite biofuel process simulation for understanding the molecular partitioning of extractives in different process streams. Model results are used to explore some implications for extractive species in the production of sugars and waste products from Douglas-fir forestry residue feedstock.
Keywords: Biomass; Bioproducts; Composition; Feedstock; Slash