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On the basis of the one strain-many compounds (OSMAC) strategy, two new cyclic thiopeptides, geninthiocins E and F, together with four known geninthiocin derivatives, geninthiocins A, B, C, and val-geninthiocin were isolated from Streptomyces sp. CPCC 200267. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and Marfey's method. Geninthiocin E (1), val-geninthiocin (3), geninthiocin A (4), and geninthiocin B (5) exhibited significant anti-influenza A virus activities with the IC values of 28.7, 15.3, 7.3, and 18.3 μM, respectively. Compounds 3 and 4 showed moderate antibacterial activities against Staphylococcus aureus.
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http://dx.doi.org/10.1038/s41429-022-00580-0 | DOI Listing |
J Ind Microbiol Biotechnol
December 2024
Manchester Institute of Biotechnology, School of Chemistry, Faculty of Science and Engineering, University of Manchester, Manchester M1 7DN, UK.
The thiopeptide GE2270A is a clinically relevant, ribosomally synthesised, and post-translationally modified peptide naturally produced by Planobispora rosea. Due to the genetically intractable nature of P. rosea, heterologous expression is considered a possible route to yield improvement.
View Article and Find Full Text PDFJ Am Chem Soc
May 2025
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Thiopeptides, which share a macrocyclic framework characterized by a six-membered, nitrogen heterocycle central to multiple (thi)azol(in)es and dehydroamino acids, represent one of the most structurally complex groups of ribosomally synthesized and post-translationally modified peptides (RiPPs). Although post-translational modifications (PTMs) necessary for common framework formation were established, how bicyclic thiopeptides, which depend on additional specific enzyme activities to afford a side ring system, are formed remains poorly understood. Using the biosynthesis of nosiheptide as a model system, here, we report the first PTM logic to achieve a bicyclic thiopeptide based on in vivo and in vitro structural reconstitution.
View Article and Find Full Text PDFJ Antibiot (Tokyo)
February 2023
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
On the basis of the one strain-many compounds (OSMAC) strategy, two new cyclic thiopeptides, geninthiocins E and F, together with four known geninthiocin derivatives, geninthiocins A, B, C, and val-geninthiocin were isolated from Streptomyces sp. CPCC 200267. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and Marfey's method.
View Article and Find Full Text PDFJ Am Chem Soc
June 2022
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Macrocyclic peptides are sought-after molecular scaffolds for drug discovery, and new methods to access diverse libraries are of increasing interest. Here, we report the enzymatic synthesis of pyridine-based macrocyclic peptides (pyritides) from linear precursor peptides. Pyritides are a recently described class of ribosomally synthesized and post-translationally modified peptides (RiPPs) and are related to the long-known thiopeptide natural products.
View Article and Find Full Text PDFBMC Microbiol
January 2022
Department of Biology, Federico II University, via Cinthia, Complesso Universitario di Monte Sant'Angelo, 80126, Naples, Italy.
Background: Members of the Bacillus genus produce a large variety of antimicrobial peptides including linear or cyclic lipopeptides and thiopeptides, that often have a broad spectrum of action against Gram-positive and Gram-negative bacteria. We have recently reported that SF214, a marine isolated strain of Bacillus pumilus, produces two different antimicrobials specifically active against either Staphylococcus aureus or Listeria monocytogenes. The anti-Staphylococcus molecule has been previously characterized as a pumilacidin, a nonribosomally synthesized lipopetide composed of a mixture of cyclic heptapeptides linked to fatty acids of variable length.
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