History of the Triticeae Symposia

The International Triticeae Symposia were initiated to encourage scientists working on different aspects of the Triticeae1 to share information and examine the distant relatives of its cereal species. There have now been seven symposia, each in a different country. The scope of these symposia is briefly reviewed. The merits of the symposium series are identified as their interdisciplinary nature and small size.     

Insect natural products and processes: new treatments for human disease

In this overview, some of the more significant recent developments in bioengineering natural products from insects with use or potential use in modern medicine are described, as well as in utilisation of insects as models for studying essential mammalian processes such as immune responses to pathogens. To date, insects have been relatively neglected as sources of modern drugs although they have provided valuable natural products, including honey and silk, for at least 4-7000 years, and have featured in folklore medicine for thousands of years. Particular examples of Insect Folk Medicines will briefly be described which have subsequently led through the application of molecular and bioengineering techniques to the development of bioactive compounds with great potential as pharmaceuticals in modern medicine. Insect products reviewed have been derived from honey, venom, silk, cantharidin, whole insect extracts, maggots, and blood-sucking arthropods. Drug activities detected include powerful antimicrobials against antibiotic-resistant bacteria and HIV, as well as anti-cancer, anti-angiogenesis and anti-coagulant factors and wound healing agents. Finally, the many problems in developing these insect products as human therapeutic drugs are considered and the possible solutions emerging to these problems are described.     

Making small molecules in plants: A chassis for synthetic biology-based production of plant natural products

Plant natural products have been extensively exploited in food,medicine,flavor,cosmetic,renewable fuel,and other industrial sectors.Synthetic biology has recently emerged as a promising means for the cost-effective and sustainable production of natural products.Compared with engineering microbes for the production of plant natural products,the potential of plants as chassis for producing these compounds is underestimated,largely due to challenges encountered in engineering plants.Knowledge in pl...     

菌物生药学——一个充满生机的边缘学科

菌物生药学是一门新兴的边缘学科,它涉及菌物学、生药学、中药学等许多学科,以菌物药为研究对象,运用现代自然科学的理论知识和技术方法,研究和探讨菌物药的来源、性状、显微特征、理化鉴别、质量指标以及引种驯化、发酵等生物工程和寻找新药源的理论和实践问题。随着现代科学尤其是现代生命科学的飞速发展,菌物药的研究在当今世界也有重要的理论和实践意义。本文从菌物生药学的发展历史,研究内容以及与其他学科关系等几个方面进行阐述,旨在将这一具有理论和实践价值的学科得以发展。     

Natural products as a screening resource

Natural products have been the most productive source of leads for new drugs, but they are currently out of fashion with the pharmaceutical industry. New approaches to sourcing novel compounds from untapped areas of biodiversity coupled with the technical advances in analytical techniques (such as microcoil NMR and linked LC-MS-NMR) have removed many of the difficulties in using natural products in screening campaigns. As the 'chemical space' occupied by natural products is both more varied and more drug-like than that of combinatorial chemical collections, synthetic and biosynthetic methods are being developed to produce screening libraries of natural product-like compounds. A renaissance of drug discovery inspired by natural products can be predicted.     

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds.     

Evolution and current status of the phytochemistry of nitrogenous compounds

Nitrogen-containing and other secondary plant products have evolved as a consequence of the struggle between the plant and the animal kingdoms, the latter directly or indirectly thriving on plants. During evolution plants developed bioactive and exceedingly complicated chemical structures that serve the purpose of plant defense. It is this property of those plants that has been exploited by mankind as medicines, poisons and recreational drugs. Three classes of nitrogen-containing plant products are being reviewed in this article: the alkaloids, the cyanogenic glucosides/glucosinolates and the nonprotein amino acids. It is the interplay of different scientific disciplines such as chemistry, pharmacognosy, medicine, analytics, cell biology, molecular biology, botany and chemotaxonomy that form a new and exciting area called "phytochemistry". It is foreseeable that this integration of disciplines across traditional borders will bring new achievements in phytochemistry, as history has taught us already.     

The synthesis and anticancer effects of a range of natural and unnatural hop β-acids on breast cancer cells

The β-acids derived from hops (Humulus lupulus L.) are polyphenols classified as lupulones. As part of our on-going interest in the pharmacognosy of these natural products we were keen to investigate the anticancer activity of lupulone 1 as well as individual lupulone congeners. To achieve this we undertook the synthesis of natural as well as unnatural lupulone derivatives and evaluated them for their anticancer activity against the breast cancer cell lines MCF-7 and MDA-MB-231.The results of our investigations revealed that all of the novel unnatural lupulone derivatives that were synthesised were found to be more toxic to MDA-MB-231 cell lines at 72 h than the parent lupulone 1 itself (except for the α-substituent R¹ was CH₃). Further investigations confirmed that the novel lupulone derivatives were very efficient at killing cancer cells by apoptosis but appear to do so in a time-dependant process. This outcome may be of great significance as MDA-MB-231 cell lines are characterised by an aggressive phenotype with a propensity to invade other tissue, to form metastases as well as an ability to become insensitive to chemotherapeutic agents.     

Stag Parties Linger: Continued Gender Bias in a Female-Rich Scientific Discipline

Discussions about the underrepresentation of women in science are challenged by uncertainty over the relative effects of the lack of assertiveness by women and the lack of recognition of them by male colleagues because the two are often indistinguishable. They can be distinguished at professional meetings, however, by comparing symposia, which are largely by invitation, and posters and other talks, which are largely participant-initiated. Analysis of 21 annual meetings of the American Association of Physical Anthropologists reveals that within the subfield of primatology, women give more posters than talks, whereas men give more talks than posters. But most strikingly, among symposia the proportion of female participants differs dramatically by the gender of the organizer. Male-organized symposia have half the number of female first authors (29%) that symposia organized by women (64%) or by both men and women (58%) have, and half that of female participation in talks and posters (65%). We found a similar gender bias from men in symposia from the past 12 annual meetings of the American Society of Primatologists. The bias is surprising given that women are the numerical majority in primatology and have achieved substantial peer recognition in this discipline.     

Survey of marine natural product structure revisions: a synergy of spectroscopy and chemical synthesis

The structural assignment of new natural product molecules supports research in a multitude of disciplines that may lead to new therapeutic agents and or new understanding of disease biology. However, reports of numerous structural revisions, even of recently elucidated natural products, inspired the present survey of techniques used in structural misassignments and subsequent revisions in the context of constitutional or configurational errors. Given the comparatively recent development of marine natural products chemistry, coincident with modern spectroscopy, it is of interest to consider the relative roles of spectroscopy and chemical synthesis in the structure elucidation and revision of those marine natural products that were initially misassigned. Thus, a tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised. Misassignments of constitution are more frequent than perhaps anticipated by reliance on HMBC and other advanced NMR experiments, especially when considering the full complement of all natural products. However, these techniques also feature prominently in structural revisions, specifically of marine natural products. Nevertheless, as is the case for revision of relative and absolute configuration, total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation. It also becomes apparent that considerable 'detective work' remains in structure elucidation, in spite of the spectacular advances in spectroscopic techniques.     

Solid phase synthesis of complex natural products and libraries thereof.

Natural products have served as an important source of medicinal compounds and pharmaceutical leads over the last century. Within the last 10 years, significant interest has developed in applying combinatorial chemistry techniques to the study of natural products and their biological activities. In this review, we examine several representative efforts wherein natural product skeletons have been constructed or immobilized on solid support and subsequently derivatized, giving rise to analog libraries useful in understanding the structure-activity relationships of the parent natural product. Issues such as target selection, library design, linker development, automation, and library characterization are addressed.     

Reappraising a decade old explanatory model for pharmacognosy

It has been a decade since a tripod model of pharmacognosy – organism, biological activity, chemical structure – was proposed. Since then advances in all disciplines have taken science into the 21st century. What are the implications for pharmacognosy? In this paper we expand the previous model, adding a new module with focus on informatics to encompass results of new technical and theoretical advancements for drug discovery.     

内生真菌天然活性产物的研究进展

药用植物内生真菌能够产生许多结构新颖的活性次级代谢产物,已成为发现新天然活性物质的重要源泉。结合作者的工作,文中通过对内生真菌天然产物的分类,对这一领域的研究进展进行综述。     

Protein engineering towards natural product synthesis and diversification

A dazzling array of enzymes is used by nature in making structurally complex natural products. These enzymes constitute a molecular toolbox that may be used in the construction and fine-tuning of pharmaceutically active molecules. Aided by technological advancements in protein engineering, it is now possible to tailor the activities and specificities of these enzymes as biocatalysts in the production of both natural products and their unnatural derivatives. These efforts are crucial in drug discovery and development, where there is a continuous quest for more potent agents. Both rational and random evolution techniques have been utilized in engineering these enzymes. This review will highlight some examples from several large families of natural products.     

Rational engineering strategies for achieving high-yield,high-quality and high-stability of natural product production in actinomycetes

Actinomycetes are recognized as excellent producers of microbial natural products, which have a wide range of applications, especially in medicine, agriculture and stockbreeding. The three main indexes of industrialization (titer, purity and stability) must be taken into overall consideration in the manufacturing process of natural products. Over the past decades, synthetic biology techniques have expedited the development of industrially competitive strains with excellent performances. Here, we summarize various rational engineering strategies for upgrading the performance of industrial actinomycetes, which include enhancing the yield of natural products, eliminating the by-products and improving the genetic stability of engineered strains. Furthermore, the current challenges and future perspectives for optimizing the industrial strains more systematically through combinatorial engineering strategies are also discussed.     

Proteomic analysis of polyketide and nonribosomal peptide biosynthesis

Polyketides and non-ribosomal peptides are in a class of natural products important both as drug sources and as dangerous toxins and virulence factors. While studies over the last two decades have provided substantial characterization of the modular synthases that produce these compounds at the genetic level, their understanding at the protein level is much less understood. New proteomic platforms called an orthogonal active site identification system (OASIS) and proteomic interrogation of secondary metabolism (PrISM) have been developed to identify and quantify natural product synthase enzymes. Reviewed here, these tools offer the means to discover and analyze modular synthetic pathways that are limited by genetic techniques, opening the tools of contemporary proteomics to natural product sciences.     

Natural,semisynthetic and synthetic tyrosinase inhibitors

Tyrosinase plays a pivotal role in the synthesis of melanin pigment synthesis on skin utilizing tyrosine as a substrate. Melanin is responsible for the protection against harmful ultraviolet irradiation, which can cause significant pathological conditions, such as skin cancers. However, it can also create esthetic problems when accumulated as hyperpigmented spots. Various skin-whitening ingredients which inhibit tyrosinase activity have been identified. Some of them, especially ones with natural product origins, possess phenolic moiety and have been employed in cosmetic products. Semi-synthetic and synthetic inhibitors have also been developed under inspiration of the natural inhibitors yet some of which have no phenolic groups. In this review, tyrosinase inhibitors with natural, semi-synthetic and synthetic origins are listed up with their structures, activities and characteristics. Further, a recent report on the adverse effect of a natural melanin synthesis inhibitor which was included in skin-whitening cosmetics is also briefly discussed.     

Lessons learned from the transformation of natural product discovery to a genome-driven endeavor

Natural product discovery is currently undergoing a transformation from a phenotype-driven field to a genotype-driven one. The increasing availability of genome sequences, coupled with improved techniques for identifying biosynthetic gene clusters, has revealed that secondary metabolomes are strikingly vaster than previously thought. New approaches to correlate biosynthetic gene clusters with the compounds they produce have facilitated the production and isolation of a rapidly growing collection of what we refer to as “reverse-discovered” natural products, in analogy to reverse genetics. In this review, we present an extensive list of reverse-discovered natural products and discuss seven important lessons for natural product discovery by genome-guided methods: structure prediction, accurate annotation, continued study of model organisms, avoiding genome-size bias, genetic manipulation, heterologous expression, and potential engineering of natural product analogs.     

Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR

Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets.This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed.     

Waste biotech

US market for environmental biotech products for waste treatment worth $261.3 M by 2013 Marine pharmacognosy Recent patents related to biowaste and bioactive compounds Project profile: Concentration and separation of bioactives in food science Microbial-based motor fuels Dairy fermentation, cell factories and bioactive peptides Earliest genetic material: Waste from the stars? Marine bacteria use carbon dioxide