Overcoming synthetic challenges in target synthesis using SmI2: recent advances

Just‐Baringo, Xavier; Yalavac, Irem; Procter, David J.

doi:10.1039/9781782623960-00001

Cited by 8 publications

(7 citation statements)

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“…29 The antibiotic activity of saalfelduracin is approximately equivalent to thiostrepton. 29,110 This study also provided insight into thioamide biosynthesis for the previously reported thioamidated thiopeptides, which include thiopeptin (from Micromonospora arborensis NRRL 8041) and Sch 18640 (Streptomyces tateyamensis ATCC 21389). 114,115 The genomes for the thiopeptide-and Sch 18640-producing organisms were sequenced, which upon analysis found ycaO-tfuA genes present in a BGC along with other anticipated thiopeptide biosynthetic genes.…”

Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 77%

“…108 Thioamidated thiopeptides-Thiazolylpeptides (or thiopeptides) are RiPP natural products with many displaying nanomolar growth suppression activity towards Grampositive human pathogens. 109,110 Thiostrepton is used as a topical agent in veterinary medicine, while LFF571, a semisynthetic analog of the thiopeptide GE2270A, displayed promising efficacy in human clinical trials against C. difficile infections. 110,111 Nosiheptide has been widely used in animal feed as a growth promoter.…”

Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 99%

“…109,110 Thiostrepton is used as a topical agent in veterinary medicine, while LFF571, a semisynthetic analog of the thiopeptide GE2270A, displayed promising efficacy in human clinical trials against C. difficile infections. 110,111 Nosiheptide has been widely used in animal feed as a growth promoter. Thiopeptides exert their antibiotic activity by inhibiting protein translation, with the exception of cyclothiazomycins (reported as RNA polymerase inhibitors) and lactazoles (no reported activity).…”

Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 99%

“…Thiopeptides exert their antibiotic activity by inhibiting protein translation, with the exception of cyclothiazomycins (reported as RNA polymerase inhibitors) and lactazoles (no reported activity). 110,112,113 A few thiopeptides have been reported that bear a thioamide group, but until recently, the origin of this group was unknown ( Figure 2). 114,115 A recent discovery of a thiopeptide from Amycolatopsis saalfeldensis NRRL B-24474 also displays a thioamide moiety.…”

Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 99%

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Biosynthesis and Chemical Applications of Thioamides

et al. 2019

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Thioamidation as a posttranslational modification is exceptionally rare, with only a few reported natural products and exactly one known protein example (methyl-coenzyme M reductase from methane-metabolizing archaea). Recently, there has been significant progress in elucidating the biosynthesis and function of several thioamide-containing natural compounds. Separate developments in the chemical installation of thioamides into peptides and proteins have enabled cell biology and biophysical studies that advance the current understanding of natural thioamides. This review highlights the various strategies used by Nature to install thioamides in peptidic scaffolds and the potential functions of this rare but important modification. We also discuss synthetic methods used for the site-selective incorporation of thioamides into polypeptides with a brief discussion of the physicochemical implications. This account will serve as a foundation for further study of thioamides in natural products and their various applications.

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Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 77%

Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 99%

Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 99%

Section: Ycao-independent Ripp Natural Productsmentioning

confidence: 99%

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Biosynthesis and Chemical Applications of Thioamides

et al. 2019

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“…96 There have been extensive investigations into the derivatization of thiopeptides with the goal of increasing activity and solubility in order to capitalize on their unique mechanism of action and potent activity. 97 Thiostrepton (Tsr), a series b thiopeptide, is the parent of this class of macrocycles. It was first isolated in 1954 from Streptomyces azureus and has subsequently been found to be produced by Streptomyces hawaiiensis and Streptomyces laurentii.…”

Section: Thiopeptidesmentioning

confidence: 99%

Fixing the Unfixable: The Art of Optimizing Natural Products for Human Medicine

Yñigez-Gutierrez

Bachmann

2019

J. Med. Chem.

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Molecules isolated from natural sources including bacteria, fungi, and plants are a long-standing source of therapeutics that continue to add to our medicinal arsenal today. Despite their potency and prominence in the clinic, complex natural products often exhibit a number of liabilities that hinder their development as therapeutics, which may be partially responsible for the current trend away from natural product discovery, research, and development. However, advances in synthetic biology and organic synthesis have inspired a new generation of natural product chemists to tackle powerful undeveloped scaffolds. In this Perspective, we will present case studies demonstrating the historical and current focus on making targeted, but significant, changes to natural product scaffolds via biosynthetic gene cluster manipulation, total synthesis, semisynthesis, or a combination of these methods, with a focus on increasing activity, decreasing toxicity, or improving chemical and pharmacological properties.

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