Lydiamycins A–D: Cyclodepsipetides with Antimycobacterial Properties

Huang, Xueshi; Roemer, Ernst; Sattler, Isabel; Moellmann, Ute; Christner, Arnulf; Grabley, Susanne

doi:10.1002/anie.200503381

Cited by 36 publications

(40 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, within numerous cyclic depsipeptides only 39 13‐membered rings can be found in the dictionary of natural products, representing seven different compound classes 4. Lydiamycin A ( 3 ) has shown antibacterial activity against a series of mycobacteria, including Mycobacterium tuberculosis 5. The beauveriolides I and III ( 4, 5 ) have an antiatherosclerotic effect in vivo and show promise as potential lead compounds for therapeutic agents 6.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Conformational Analysis of Stevastelin C3 Analogues and Their Activity Against the Dual‐Specific Vaccina H1‐Related Phosphatase

Bisek

Wetzel

Arndt

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

The biological activity of macrocyclic natural products depends on their conformational properties. For both the elucidation of enzyme binding affinities as well as the development of selective drugs, rigid macrocyclic scaffolds carry high potential. In this study, 13-membered cyclodepsipeptides based on the structure of naturally occurring stevastelins were studied in detail. Six diastereomeric stevastelin C3 analogues and four phosphorylated derivatives were synthesized. The synthesis of linear precursors was achieved on solid support by starting from stereoisomerically pure 2-methyl-3-hydroxy acids. Subsequent macro-lactamization gave the cyclic depsipeptides in very good yields (36-62%). The conformational space of these stevastelin C3 analogues was computationally investigated. On the basis of NMR spectroscopic data, homogeneous conformations were determined for each benzylated depsipeptide and the influence of phosphorylation on the overall conformation was investigated. Importantly, phosphorylation was found to significantly weaken the conformational preferences of the 13-membered depsipeptides. Finally, the cyclic depsipeptides were tested for activity against phosphatases. Inhibitory activity on vaccina H1-related phosphatase was observed depending on the derivatization of the cycles. The activity profiles are discussed in the light of the structural data.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis and Conformational Analysis of Stevastelin C3 Analogues and Their Activity Against the Dual‐Specific Vaccina H1‐Related Phosphatase

Bisek

Wetzel

Arndt

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Piperazic acid is an attractive building block of many complex secondary metabolites such as Antrimycin [52], Chloptosin [53], Himastatin [39], Luzopeptin [54], Quinoxapeptin [55], Lydiamycin [56], Piperazimycin [57] and Sanglifehrin [58]. The detailed biosynthetic mechanisms by which piperazic acid are formed are not well understood.…”

Section: Resultsmentioning

confidence: 99%

Identification and characterization of the biosynthetic gene cluster of polyoxypeptin A, a potent apoptosis inducer

Wang

Huang

et al. 2014

BMC Microbiol

View full text Add to dashboard Cite

BackgroundPolyoxypeptin A was isolated from a culture broth of Streptomyces sp. MK498-98 F14, which has a potent apoptosis-inducing activity towards human pancreatic carcinoma AsPC-1 cells. Structurally, polyoxypeptin A is composed of a C15 acyl side chain and a nineteen-membered cyclodepsipeptide core that consists of six unusual nonproteinogenic amino acid residues (N-hydroxyvaline, 3-hydroxy-3-methylproline, 5-hydroxypiperazic acid, N-hydroxyalanine, piperazic acid, and 3-hydroxyleucine) at high oxidation states.ResultsA gene cluster containing 37 open reading frames (ORFs) has been sequenced and analyzed for the biosynthesis of polyoxypeptin A. We constructed 12 specific gene inactivation mutants, most of which abolished the production of polyoxypeptin A and only ΔplyM mutant accumulated a dehydroxylated analogue polyoxypeptin B. Based on bioinformatics analysis and genetic data, we proposed the biosynthetic pathway of polyoxypeptin A and biosynthetic models of six unusual amino acid building blocks and a PKS extender unit.ConclusionsThe identified gene cluster and proposed pathway for the biosynthesis of polyoxypeptin A will pave a way to understand the biosynthetic mechanism of the azinothricin family natural products and provide opportunities to apply combinatorial biosynthesis strategy to create more useful compounds.

show abstract

“…All isolated cyclodepsipeptides were shown to selectively inhibit Mycobacterium smegmatis SG 987, M. aurum SB66, and M. vaccae IMET 10670 in a panel of Gram-positive and Gram-negative bacteria, yeasts, and fungi (Huang et al, 2006).…”

Section: Lydiamycinsmentioning

confidence: 99%

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

Dembitsky¹

2017

Int. J. Curr. Res. Biosci. Plant Biol.

View full text Add to dashboard Cite

A b s t r a c t A r t i c l e I n f oThis review is a comprehensive survey of unique, unusual, and rare fatty acids incorporated into natural marine and terrestrial peptides obtained from fungi, fungal endophytes, lichenized ascomycetes, basidiomycetes, and actinomycetes. Lots of fungal peptides display important biological activities of interest, which includes antitumor, antibacterial, antimicrobial, antifungal, phototoxic, HIV inhibitory, immunosuppressive properties, and other pharmacological activities. There is no doubt that they are of great importance, especially in medicinal chemistry and/or pharmaceutical application. This review presents structures of more than 150 fatty acids, incorporated into marine and terrestrial fungal lipopeptides.

show abstract

Lydiamycins A–D: Cyclodepsipetides with Antimycobacterial Properties

Cited by 36 publications

References 18 publications

Synthesis and Conformational Analysis of Stevastelin C3 Analogues and Their Activity Against the Dual‐Specific Vaccina H1‐Related Phosphatase

Synthesis and Conformational Analysis of Stevastelin C3 Analogues and Their Activity Against the Dual‐Specific Vaccina H1‐Related Phosphatase

Identification and characterization of the biosynthetic gene cluster of polyoxypeptin A, a potent apoptosis inducer

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

Contact Info

Product

Resources

About