Total synthesis offers a key approach to the production of natural medicines if sufficient quantities cannot be obtained due to low natural abundance or lack of efficient fermentation or semi-synthesis methods. This Viewpoint outlines the previous and current states of research as they apply to the total synthesis of natural medicines on an industrial scale and provides a holistic view on the potential for future developments in the field.
Covering literature to December 2022
This review provides a comprehensive account of all natural products (500 compounds, including 17 semi-synthetic derivatives) described in the primary literature up to December 2022, reported to be capable of inhibiting the egg hatching, motility, larval development and/or the survival of helminths (i.e., nematodes, flukes and tapeworms). These parasitic worms infect and compromise the health and welfare, productivity and lives of commercial livestock (i.e., sheep, cattle, horses, pigs, poultry and fish), companion animals (i.e., dogs and cats) and other high value, endangered and/or exotic animals. Attention is given to chemical structures, as well as source organisms and anthelmintic properties, including the nature of bioassay target species, in vivo animal hosts, and measures of potency.
Covering: 2010 to 2023
Floral volatiles are a chemically diverse group of plant metabolites that serve multiple functions. Their composition is shaped by environmental, ecological and evolutionary factors. This review will summarize recent advances in floral scent research from chemical, molecular and ecological perspectives. It will focus on the major chemical classes of floral volatiles, on notable new structures, and on recent discoveries regarding the biosynthesis and the regulation of volatile emission. Special attention will be devoted to the various functions of floral volatiles, not only as attractants for different types of pollinators, but also as defenses of flowers against enemies. We will also summarize recent findings on how floral volatiles are affected by abiotic stressors, such as increased temperatures and drought, and by other organisms, such as herbivores and flower-dwelling microbes. Finally, this review will indicate current research gaps, such as the very limited knowledge of the isomeric pattern of chiral compounds and its importance in interspecific interactions.
Covering: up to the end of July, 2023
1,2-Oxazine is a heterocyclic scaffold rarely found in natural products and is characterized by a directly connected N–O bond in a six-membered ring. Since the discovery of geneserine, the first 1,2-oxazine-containing natural product (1,2-oxazine NP) being isolated from Calabar bean (Physostigma venenosum) in 1925, a total of 76 naturally occurring 1,2-oxazine NPs have been isolated and identified from various sources, which have attracted the attention of researchers in the field of natural product chemistry, organic synthesis, biosynthesis, and pharmacology. This review summarizes the chemical family of 1,2-oxazine NPs, focusing on their source organisms, structural diversities, chemical synthesis, and biosynthesis.
Covering: 2012 to 2023
The human population is aging. Thus, the greatest risk factor for numerous diseases, such as diabetes, cancer and neurodegenerative disorders, is increasing worldwide. Age-related diseases do not typically occur in isolation, but as a result of multi-factorial causes, which in turn require holistic approaches to identify and decipher the mode of action of potential remedies. With the advent of C. elegans as the primary model organism for aging, researchers now have a powerful in vivo tool for identifying and studying agents that effect lifespan and health span. Natural products have been focal research subjects in this respect. This review article covers key developments of the last decade (2012–2023) that have led to the discovery of natural products with healthy aging properties in C. elegans. We (i) discuss the state of knowledge on the effects of natural products on worm aging including methods, assays and involved pathways; (ii) analyze the literature on natural compounds in terms of their molecular properties and the translatability of effects on mammals; (iii) examine the literature on multi-component mixtures with special attention to the studied organisms, extraction methods and efforts regarding the characterization of their chemical composition and their bioactive components. (iv) We further propose to combine small in vivo model organisms such as C. elegans and sophisticated analytical approaches (“wormomics”) to guide the way to dissect complex natural products with anti-aging properties.
Time span of literature covered: up to mid-2023
Iterative type I polyketide synthases (iPKSs) are outstanding natural chemists: megaenzymes that repeatedly utilize their catalytic domains to synthesize complex natural products with diverse bioactivities. Perhaps the most fascinating but least understood question about type I iPKSs is how they perform the iterative yet programmed reactions in which the usage of domain combinations varies during the synthetic cycle. The programmed patterns are fulfilled by multiple factors, and strongly influence the complexity of the resulting natural products. This article reviews selected reports on the structural enzymology of iPKSs, focusing on the individual domain structures followed by highlighting the representative programming activities that each domain may contribute.
Covering: 2011–2022
The low amounts of terpenoids produced in plants and the difficulty in synthesizing these complex structures have stimulated the production of terpenoid compounds in microbial hosts by metabolic engineering and synthetic biology approaches. Advances in engineering yeast for terpenoid production will be covered in this review focusing on four directions: (1) manipulation of host metabolism, (2) rewiring and reconstructing metabolic pathways, (3) engineering the catalytic activity, substrate selectivity and product specificity of biosynthetic enzymes, and (4) localizing terpenoid production via enzymatic fusions and scaffolds, or subcellular compartmentalization.
A personal selection of 32 recent papers is presented, covering various aspects of current developments in bioorganic chemistry and novel natural products, such as clavirolide L from Clavularia viridis.
Covering: up to 2023
Short-chain dehydrogenase/reductases (SDR) are known to catalyze the regio- and stereoselective reduction of a variety of substrate types. Investigations of the deoxygenation of emodin to chrysophanol has led to the discovery of the anthrol reductase activity of an SDR, MdpC involved in monodictyphenone biosynthesis of Aspergillus nidulans and provided access to (R)-dihydroanthracenone, a putative biosynthetic intermediate. This facilitated the identification of several MdpC-related enzymes involved in the biosynthesis of aflatoxins B1, cladofulvin, neosartorin, agnestins and bisanthraquinones. Because of their ability to catalyze the reduction of hydroanthraquinone (anthrols) using NADPH, they were named anthrol reductases. This review provides a comprehensive summary of all the anthrol reductases that have been identified and characterized in the last decade along with their role in the biosynthesis of natural products. In addition, the applications of these enzymes towards the chemoenzymatic synthesis of flavoskyrins, modified bisanthraquinones, 3-deoxy anthraquinones, chiral cycloketones and β-halohydrins have been discussed.
Covering: up to the end of 2022
The area of scalemic natural products is often enigmatic from a mechanistic standpoint, since low optical purity is observed in compounds having multiple contiguous stereogenic centers resulting from mechanistically distinct biogenetic steps. A scalemic state is rarely the result of a sloppy enzymatic activity, rather resulting from the expression of antipodal enzymes/directing proteins or from the erosion of optical purity by enzymatic or spontaneous reactions. Evidence for these processes is critically reviewed, identifying the mechanisms most often associated to the enzymatic generation of scalemic natural products and also discussing analytical exploitations of natural products' scalemicity.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：