scholarly journals Making drugs out of sunlight and ‘thin air’: an emerging synergy of synthetic biology and natural product chemistry

2020 ◽  
Vol 42 (4) ◽  
pp. 34-39
Author(s):  
Michael J. Stephenson ◽  
Anne Osbourn
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Natural Product ◽  
Large Scale ◽  
Production Systems ◽  
Biological Activities ◽  
Structural Complexity ◽  
Scale Production ◽  
Natural Product Chemistry ◽  
Product Chemistry

Nature has long served as a rich source of structurally diverse small organic molecules with medicinally relevant biological activities. Despite the historical success of these so-called natural products, the enthusiasm of big pharma to explore these compounds as leads in drug design has waxed and waned. A major contributor to this is their often inherent structural complexity. Such compounds are difficult (often impossible) to access synthetically, a hurdle that can stifle lead development and hinder sustainable large-scale production of promising leads for clinical evaluation. However, in recent years, an emerging synergy between synthetic biology and natural product chemistry offers the potential for a renaissance in our ability to access natural products for drug discovery and development. Advances in genome sequencing, bioinformatics and the maturing of heterologous expression platforms are increasing, enabling the study, and ultimately, the manipulation of plant biosynthetic pathways. The triterpenes are one of the most structurally diverse families of natural products and arguably one of the most underrepresented in the clinic. The plant kingdom is the richest source of triterpene diversity, with >20,000 triterpenes reported so far. Transient expression of genes for candidate enzymes and pathways in amenable plant species is emerging as a powerful and rapid means of investigating and harnessing the plant enzymes involved in generating this diversity. Such platforms also have the potential to serve as production systems in their own right, with the possibility of upscaling these discoveries into commercially useful products using the same overall basic procedure. Ultimately, the carbon source for generation of high-value compounds in plants is photosynthesis. Therefore, we could, with the help of plants, be producing new medicines out of sunlight and ‘thin air’ in green factories in the not too distant future.

Recent advances in the synthesis of oxaspirolactones and their application in the total synthesis of related natural products

2019 ◽  
Vol 17 (31) ◽  
pp. 7270-7292 ◽  
Author(s):  
Sagar S. Thorat ◽  
Ravindar Kontham
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Medicinal Chemistry ◽  
Natural Product Chemistry ◽  
Structural Motifs ◽  
Recent Advances ◽  
Synthetic Molecules ◽  
Product Chemistry

Oxaspirolactones are ubiquitous structural motifs found in natural products and synthetic molecules with a diverse biochemical and physicochemical profile, and represent a valuable target in natural product chemistry and medicinal chemistry.

scholarly journals Solvent Derived Artifacts in Natural Products Chemistry

2009 ◽  
Vol 4 (3) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
Federica Maltese ◽  
Frank van der Kooy ◽  
Robert Verpoorte
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Chemical Reactions ◽  
Critical Role ◽  
Total Yield ◽  
Purification Method ◽  
Active Compounds ◽  
Natural Product Chemistry ◽  
Extraction And Purification ◽  
Product Chemistry

Solvents play an important and critical role in natural product chemistry. They are mainly used during the extraction and purification of metabolites from a biological matrix. To a lesser extent, solvents are also used as reagents or catalysts to perform chemical reactions. This review focuses on the most important classes of solvents, including alcohols, halogen-containing solvents, esters, ethers, acids and bases. The chemical reactions associated with the use of these solvents to form the so-called “artifacts” are discussed and the most common contaminants found in these solvents are also reviewed. The formation of artifacts and the use of contaminated solvents mainly leads to the formation of new compounds, loss of activity of active compounds, formation of active compounds from inactive ones (false positives), loss in total yield of important compounds during isolation, formation of toxic compounds and difficulty in reproducing an extraction or purification method. Finally, the need for stability studies of purified natural products is emphasized, as this is a common overlooked aspect in natural product chemistry.

scholarly journals Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

2015 ◽  
Vol 81 (13) ◽  
pp. 4339-4350 ◽  
Author(s):  
Qi Zhang ◽  
James R. Doroghazi ◽  
Xiling Zhao ◽  
Mark C. Walker ◽  
Wilfred A. van der Donk
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Gene Cluster ◽  
Posttranslational Modifications ◽  
Large Scale ◽  
Biological Activities ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Content Type ◽  
Modified Peptides

ABSTRACTLanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthipeptides are widely distributed in taxonomically distant species, and their currently known biosynthetic systems and biological activities are diverse. Building on the recent natural product gene cluster family (GCF) project, we report here large-scale analysis of lanthipeptide-like biosynthetic gene clusters fromActinobacteria. Our analysis suggests that lanthipeptide biosynthetic pathways, and by extrapolation the natural products themselves, are much more diverse than currently appreciated and contain many different posttranslational modifications. Furthermore, lanthionine synthetases are much more diverse in sequence and domain topology than currently characterized systems, and they are used by the biosynthetic machineries for natural products other than lanthipeptides. The gene cluster families described here significantly expand the chemical diversity and biosynthetic repertoire of lanthionine-related natural products. Biosynthesis of these novel natural products likely involves unusual and unprecedented biochemistries, as illustrated by several examples discussed in this study. In addition, class IV lanthipeptide gene clusters are shown not to be silent, setting the stage to investigate their biological activities.

Revised Section F: Natural products and related compounds

1999 ◽  
Vol 71 (4) ◽  
pp. 587-643 ◽  
Author(s):  
P. M. Giles
Keyword(s):  
Organic Chemistry ◽  
Natural Products ◽  
Natural Product ◽  
Natural Product Chemistry ◽  
Structural Relationships ◽  
The Creation ◽  
Related Compounds ◽  
Single Set ◽  
Product Chemistry

The nomenclature of natural products has suffered from much confusion, mostly for historical reasons. The isolation of a new substance, in the early days of the science, generally preceded its characterization by a lengthy period. Thus, these compounds were often assigned trivial names that gave no indication of the structure of the molecule and were often found afterwards to be misleading. Even when the original names were later revised (for example: glycerin to glycerol) the new names often expressed the structure imperfectly and were thus unsuitable for the nomenclatural manipulation that is required to name derivatives or stereoisomers. The result was a proliferation of trivial names that taxed the memory of chemists and obscured important structural relationships.The resultant disorder in the literature led to the creation of committees of specialists with the task of codifying the naming of compounds in various connected areas of natural-product chemistry, such as steroids, lipids, and carbohydrates. As far as their recommendations have been followed, their efforts have been successful in eliminating confusing or duplicate nomenclature.It is the aim of the lUPAC Commission on Nomenclature of Organic Chemistry to unite as far as possible all the specialist reports into a single set of recommendations that can be applied in most areas of natural-product chemistry. Accordingly, provisional recommendations were prepared and published as Section F of the lUPAC Organic Nomenclature Rules, first in 1976, and then in the 1979 edition of the Rules.

scholarly journals Synthetic organic chemistry in China: building on an ancient tradition—an interview with Qi-Lin Zhou and Xiaoming Feng

2017 ◽  
Vol 4 (3) ◽  
pp. 437-440
Author(s):  
Philip Ball
Keyword(s):  
Organic Chemistry ◽  
Natural Products ◽  
Natural Product ◽  
Organic Synthesis ◽  
Anticancer Agents ◽  
Natural Product Synthesis ◽  
Chiral Molecules ◽  
Alternative Source ◽  
Natural Product Chemistry ◽  
Product Chemistry

Abstract If the core of chemistry is making molecules, then the construction of those found in nature—natural products—has long been regarded as one of the highest forms of the art in synthesis. These molecules, produced by living organisms for a variety of purposes, are a key source of pharmaceuticals such as antibiotics and anticancer agents. The medicinal value of natural products has been known for centuries via herbal treatments, and such compounds are still collected, refined and screened for potential drugs today, sometimes being identified from local ‘folk medicine’ practices. By identifying the active ingredients of natural extracts used in traditional medicine, chemists can then synthesize modified forms that may be even more active: this was how the analgesic aspirin was first identified as a derivative of the plant hormone salicylic acid from willow bark. As well as offering such derivatives, natural-product synthesis in organic chemistry can potentially provide a more plentiful alternative source of natural products that are available in only tiny amounts from their natural sources. Efforts to devise cheap and efficient synthetic strategies for molecules such as paclitaxel (Taxol, an anticancer agent present in the Pacific yew) and artemisinin (an anti-malarial extracted from the herb sweet wormwood, qinghao (青蒿), and recognized by the 2015 Nobel Prize for Medicine) are still on-going to satisfy global demand. Organic synthesis is about much more than making natural products: it contributes, for example, to catalysis, polymer chemistry, food science and the development of wholly synthetic drugs. Yet efforts to make complex natural products may supply a motivational testing ground for developing new synthetic techniques with broader applications. Indeed, many chemists prize the discovery of a new synthetic method above the recreation of some complex natural molecule: it is the means, not the end, that matters. The field of organic and natural-product synthesis has a strong history in China, where there is a long tradition of herbal medicine. The use of the qinghao extract for treating malaria is first recorded in AD 340, in a manual that the 2015 Nobel laureate Tu Youyou says she consulted for clues about isolating the compound in the beginning of 1970s. Some say that, in the past decade, Chinese natural-product chemistry has entered a ‘golden era’ (Zheng Q-Y and Li A. Sci China Chem 2016;59: 1059–60). Qi-Lin Zhou of Nankai University and Xiaoming Feng of Sichuan University have been at the forefront of this upsurge. Both of them have developed methods for making so-called chiral molecules: arrangements of atoms that have a handedness, so that they can exist in two mirror-image versions. Natural products typically are chiral molecules, and their biological activity may depend on having the correct handedness. The selective synthesis of chiral molecules (asymmetric synthesis) is therefore vital to natural-product chemistry, and typically involves the use of catalysts that are chiral themselves. National Science Review spoke to Zhou and Feng about their work and their perspectives on organic synthesis in China. Qi-Lin Zhou of College of Chemistry at Nankai University, China. (Courtesy of Q Zhou)

scholarly journals Natural Product Chemistry of Gorgonian Corals of Genus Junceella–Part III

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 339 ◽  
Author(s):  
Hsu-Ming Chung ◽  
Yi-Chen Wang ◽  
Chung-Chih Tseng ◽  
Nan-Fu Chen ◽  
Zhi-Hong Wen ◽  
...  
Keyword(s):  
Natural Products ◽  
Pacific Ocean ◽  
Natural Product ◽  
Natural Product Chemistry ◽  
Gorgonian Corals ◽  
Product Chemistry ◽  
New Metabolites

The structures, names, bioactivities, and references of 82 natural products, including 48 new metabolites, purified from the gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from Junceella fragilis, Junceella gemmacea, Junceella juncea, and Junceella sp., collected from tropical Indo-Pacific Ocean. Some of these compounds exhibited potential biomedical activities.

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