Phytochemistry Reviews (v.12, #2)

Structural and biochemical perspectives in plant isoprenoid biosynthesis by Sangita Kumari; Piyush Priya; Gopal Misra; Gitanjali Yadav (255-291).
The isoprenoid family represents one of the most ancient and widespread classes of structurally and functionally rich biomolecules known to man. Although these natural products are synthesized in all organisms, the plant kingdom exhibits tremendous variation in their chemistry and roles, ranging from primary metabolism to secondary metabolism and specialized ecological interactions with the environment. Despite enormous diversity in structure and function, all isoprenoids are derived from the universal C5 precursor isoprene. The isoprenoid biosynthetic pathway has three major stages, viz., (1) synthesis of the isoprene building blocks, followed by their (2) assembly into flexible linear and branched hydrocarbon substrates, which then undergo (3) multistep reaction cascades to generate the vast assortment of isoprenoid end products. One of the most interesting aspects of isoprenoid biosynthesis is its being finely tuned by a multilayered and complex regulatory network, which excellently controls the machinery producing one of the most heterogeneous groups of molecules in plants. Terpene synthases, enzymes of the final stage, are key players in the generation of isoprenoid diversity, catalyzing one of the most complex reactions known to chemistry and biology. Unraveling the mechanism by which a minimal pool of substrates is thus converted into tens of thousands of regiospecific and stereospecific products, is a promising research avenue: This knowledge may be practically used for rational design of novel compounds by metabolic engineering, in order to yield plants with improved nutritional efficacy, stress resistance, bio-pharmaceutical properties etc. This review is an attempt to summarize the biochemical, molecular, physiological, structural, genomic and evolutionary aspects of isoprenoid biosynthesis, providing new insights into how these enzymes utilize various innovative strategies for creation of the so-called final terpenome.
Keywords: Diterpene cyclases; Isoprenoid diversity; Mevalonate pathway; Non-mevalonate pathway; Prenyl transferases

Metabolomics for the rapid dereplication of bioactive compounds from natural sources by Nancy Dewi Yuliana; Muhammad Jahangir; Robert Verpoorte; Young Hae Choi (293-304).
The introduction of high throughput screening in the 1990s aimed to shorten the drugs discovery route. To fully use its high potential, this technology requires a large number of compounds to screen. Thus, increasing the number of chemicals for initial screening is high on the agenda of pharmaceutical companies. High throughput synthesis and combinatorial chemistry were developed to address this demand. However, these technologies cannot fulfill the expectation to increase new lead compounds. One of the reasons is that the obtained compounds lack relevant chemical diversity. On the other hand, it is well known that an enormous molecular diversity and biological functionality are two important features which distinguish plant extracts as a drug source from synthetic chemicals, although a natural products-based drug discovery project also poses some challenges, mostly connected with the presence of an active compound in a complex matrix with all kind of compounds. An elaborative purification to isolate and identify active compounds is thus needed. The possibility of antagonism or synergism between metabolites present in the extracts, and the fact that some common plant products have been found to be active in a number of test systems even make lead finding projects from natural sources become complicated. This review summarizes recent studies reporting metabolomics based techniques to uncover activity related compounds in complex plant matrices.
Keywords: Chromatography; Drugs discovery; Medicinal plants; Metabolomics; NMR

Grayanoids, occurring exclusively in Ericaceae plants, are well-known highly toxic components from the genera Rhododendron, Pieris, Leucothoe, Craibiodendron, Lyonia, Kalmia, etc. Grayanoids have been the topic of research in many phytochemical and pharmacological laboratories due to their complex structures and fascinating bioactivities. This review, citing 100 references, summarises their chemistry, including the total synthesis and bioactivity of grayanoids isolated from the Ericaceae family in the last five decades, to illustrate the chemo-diversity and biological significance of these diterpenoids.
Keywords: Grayanoid; Diterpenoid; Structure; Bioactivity

Enzymatic glycosylation of terpenoids by Francisco Rivas; Andres Parra; Antonio Martinez; Andres Garcia-Granados (327-339).
A significant number of terpenoid compounds are glycosides with the sugars linked to the active groups. Sometimes, the glycosidic residue is crucial for their activity, but in other cases glycosylation only improves pharmacokinetic parameters. Enzymatic glycosylation of terpenoids is a useful tool due to the high selectivity and the mildness of the reaction conditions, in comparison with chemical methods. Several types of biocatalysts have been used in the enzymatic glycosylation of terpenoids. These include the use of glycosyltransferases, trans-glycosidases, and whole-cell biotransformation systems capable of regenerating the cofactor, such as fungi, bacteria, plant-cell cultures, etc. Many biosynthesized terpenoid glycosides display medicinal and pharmacological properties and can be used as pro-drug substances. These terpenoid glycosides have also been employed as food additives (e.g. low-caloric sweetener compounds) and cosmetics, and even have applications as controlled-release fragrances.
Keywords: Biotransformation; Filamentous fungi; Glycosidase; Glycosyltransferase; Plant-cell culture

Chemistry, bioactivity and quality control of Dendrobium, a commonly used tonic herb in traditional Chinese medicine by Jun Xu; Quan-Bin Han; Song-Lin Li; Xiao-Jia Chen; Xiao-Ning Wang; Zhong-Zhen Zhao; Hu-Biao Chen (341-367).
The fresh or dried stems of many Dendrobium species are well known as one of the most expensive tonics in traditional Chinese medicine. Documented as a “superior grade” herbal medicine in the ancient text “Shen Nong’s Herbal Classic”, Dendrobium has been used for thousands of years and is now a popular health food worldwide. The main chemical components of Dendrobium are alkaloids, aromatic compounds, sesquiterpenoids and polysaccharides, with multiple biological activities, including immunomodulatory, neuroprotective and anti-tumor effects, etc. Various qualitative and quantitative methods have been developed for the quality evaluation of Dendrobium. In this review, the research progress since the 1930s relating to the chemistry, bioactivity and quality control of Dendrobium is summarized, existing problems and prospects are also discussed.
Keywords: Dendrobium ; Chemistry; Bioactivity; Quality control