Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• modifications have been observed during the maturation of different RiPPs. One example is the biosynthesis of thiopeptide GE2270, which is produced by the actinomycete Planobispora rosea ATCC53733 as a complex of related metabolites that differ in the number of methyl groups installed on the macrocyclic core

• relaxed substrate specificity for all maturases in the aer BGC: All hybrid precursors were extensively modified with dehydrations, C-methylation, N-methylations, and epimerisations comparable to the AerA precursor [112][113]. PbtM1 from the thiopeptide GE2270 BGC is another example of a side chain amide-N

• encoded in the pbt cluster of P. rosea. The thiopeptide GE2270 encoded by pbt undergoes further regioselective modification through C-methylation of thiazoles. The two rSAM MTs PbtM2 and PbtM3 methylate thiazole E and thiazole D, respectively [64]. PbtM2 and PbtM3 show substantial sequence similarities to

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• was much lower (2.6:1 and 1:1, respectively). Acid hydrolysis of 64 gave (4S)-4-hydroxy-L-glutamic acid [(2S,4S)-3] as the hydrochloride, however, its enantiomeric purity was not checked. In connection with the total synthesis of thiopeptide antibiotic nosiheptide an orthogonally protected (4S)-4

• incorporated into the thiopeptide antibiotic nosiheptide. The total synthesis of biphenomycin B relied on installation of a five-membered chain derived from a protected tert-butyl (2S,4R)-4-hydroxypyroglutamate [115]. While the protected methyl (2S,4S)-4-hydroxypyroglutamate formed a basis for the construction

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• as readily available starting material. Keywords: antibiotic; bromination; BSC; C–H arylation; cross-coupling; Hantzsch synthesis; thiopeptide; Introduction Thiopeptide antibiotics are a class of peptide-derived macrocycles which contain many thiazole and thiazoline units, with almost 90 structures

• inhibit bacterial protein synthesis through two main modes of action, most of them bind the complex of 23S rRNA with ribosomal protein L11 and few of them such as the thiopeptide of D-series GE2270 modify the action of elongation factors Tu. The most pharmalogically-advanced thiopeptide antibody of D

• heterocyclic core of the D-series thiopeptide antibiotic GE2270 was prepared. The synthetic strategy that combines direct C–H arylation, Borylation Suzuki–Miyaura cross-coupling (BSC) and Hantzsch thiazole synthesis methods proved to be highly effective regarding the fair 22% yield over 7 synthetic steps from

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• hydrolysis and disulphide bond formation through to the complex remodelling of almost every amino acid in a molecule. For example, thiopeptide antibiotics [15] and the marine toxin polytheonamide [16] were both believed to be non-ribosomal peptides for a number of years, while the bacterial cofactor

• actively transcribed thiopeptide gene clusters in human microbiota from every body site assessed [6]. Thiazoles in thiopeptides are introduced by a BCD-protein system described previously, while threonine and serine residues are dehydrated by lantibiotic-like dehydratases. The formation of core pyridine

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• . Natural products of bacteria containing a pyridine ring are rare. As an example, 1-(2-pyridinyl)ethanone was identified as a volatile of Enterobacter agglomerans [20]. Highly substituted pyridine derivatives can be found in bacterial thiopeptide antibiotics [21]. The streptopyridines of Streptomyces sp

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• thiopeptide 3 [37], easily obtained by thio-Ugi reaction in excellent yield. The reaction was very fast and was finished already after 15 min, and peptide 3 crystallized directly from the reaction mixture. Because our first attempts to couple 3 directly with amines to the corresponding amidine 5 failed [43

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• the ψ[CS-NH] thioamide bond, we started a program aimed at exploring how thiopeptide groups may affect folding and the related biophysical/biochemical activities of the membrane-active peptaibiotics [45]. This class of compounds represents a subject of long-standing, relevant, interest to our research