Total structure of the polythiazole-containing antibiotic micrococcin P. A 13C nuclear magnetic resonance study

Walker, James M.; Olesker, Alain; Valente, Lydia; Rabanal, Rosa M.; Lukacs, Gabor

doi:10.1039/c39770000706

Cited by 51 publications

(33 citation statements)

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“…3) is a macrocyclic peptide antibiotic of the thiocillin-thiazolyl class (8,9,13,25,32,54). Recently, a complete synthesis was published by Okumura et al (34).…”

Section: Discussionmentioning

confidence: 99%

The Macrocyclic Peptide Antibiotic Micrococcin P₁Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese

Carnio

Höltzel

Rudolf

et al. 2000

Appl Environ Microbiol

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Staphylococcus equorum WS 2733 was found to produce a substance exhibiting a bacteriostatic effect on a variety of gram-positive bacteria. The metabolite was purified to homogeneity by ammonium sulfate precipitation and semipreparative reversed-phase high-performance liquid chromatography. Electrospray mass spectrometry confirmed the high purity of the compound and revealed a molecular mass of 1,143 Da. By twodimensional nuclear magnetic resonance spectroscopy the substance was identified as micrococcin P 1 which is a macrocyclic peptide antibiotic that has not yet been reported for the genus Staphylococcus. A total of 95 out of 95 Listeria strains and 130 out of 135 other gram-positive bacteria were inhibited by this substance, while none of 37 gram-negative bacteria were affected. The antilisterial potential of this food-grade strain as a protective starter culture was evaluated by its in situ application in cheese-ripening experiments under laboratory conditions. A remarkable growth reduction of Listeria monocytogenes could be achieved compared to control cheese ripened with a nonbacteriocinogenic type strain of Staphylococcus equorum. In order to prove that inhibition was due to micrococcin P 1 , a micrococcin-deficient mutant was constructed which did not inhibit L. monocytogenes in cheese-ripening experiments.

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“…3) is a macrocyclic peptide antibiotic of the thiocillin-thiazolyl class (8,9,13,25,32,54). Recently, a complete synthesis was published by Okumura et al (34).…”

Section: Discussionmentioning

confidence: 99%

The Macrocyclic Peptide Antibiotic Micrococcin P₁Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese

Carnio

Höltzel

Rudolf

et al. 2000

Appl Environ Microbiol

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“…20 d (7) 7.12d--*o 4.92dq-->q(7) 1. 52 d (7) . Multiplicity changes on 2H-exchange are indicated by ~; complete disappearance of an active hydrogen is designated by s -o or d -> o .…”

Section: Pipmentioning

confidence: 99%

Total structure of the highly modified peptide antibiotic components of thiopeptin.

Hensens¹,

Albers-Schönberg²

1983

J. Antibiot.

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On the basis of 'H and 13C NMR evidence, the structures of two series of the highly modified sulfur-containing peptide antibiotic thiopeptin were elucidated.The thiopeptins produced by Streptomyces tateyamensis belong to a group of highly modified sulfur containing peptide antibiotics'), the structures of several having only recently been determined by X-ray crystallography or physical methods=`'). They inhibit primarily Gram-positive bacteria'> and exhibit no significant differences in their inhibition of protein synthesis in cell-free Escherichia coli10). Thiopeptin B, the major component is valuable as a feed-additive because of its marked growth promoting action in swine and chickens11) and was recently shown to be effective as a lactic-acidosis preventive in sheep and cattle12).Thiopeptin B and four minor components A,, A, A> and A, were characterized by MIYAIRI et al.9.13) and shown primarily by acid hydrolysis experiments") to be closely related to the antibiotic thiostrepton, whose structure, with the exception of the side chain, was determined by X-ray crystallography by ANDERSON and coworkers-2). TORi et al.,3) from a "C NMR study of the antibiotic, proposed a sequence consisting of two dehydroalanine (Deala) residues for the side chain which was subsequently confirmed by our own 'H NMR study at 300 MHz (see preceding paper). Of the spectroscopic techniques available to us it soon became apparent that only 'H and 1>C NMR spectroscopy were to be potentially useful in the structural elucidation of the thiopeptins. The molecules were not sufficiently volatile to yield a molecular ion even under field-desorption conditions and only a fragment involving the dihydroquinoline moiety and adjacent peptide was identifiable (see below). Moreover, despite the fact that some of the a components were obtained in crystalline form, they were found not to be suitable for X-ray crystallography. A strategy, involving 'H NMR comparison with thiostrepton, was therefore adopted in order to delineate their structural differences. Pertinent details of confirmatory 1>C NMR evidence are also discussed") whereas a full discussion of the 11C NMR assignments is the subject of a companion paper. Results and DiscussionThiopeptin components were separated by silica gel chromatography similar to that previously described') and found to be homogeneous by TLC. 'H NMR analysis of the components from various batches however, indicated a two compound system in the majority of cases which was confirmed by HPLC. Consistent differences in the 'H NMR spectra allowed them to be grouped into two distinct series arbitrarily designated by the subscripts a and b and some of their physical and chemical properties are summarized in Table 1. In some batches all components from the a series and only Al,, from the b

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“…Even now some structural uncertainties remain, no more so than in the case of micrococcin itself, the first thiopeptide to be isolated in 1948, and one of the first to attract the attention of synthetic organic chemists. The structure of a substance known as micrococcin P was first investigated by Walker and co-workers, [18][19][20][21][22] but following the discovery that micrococcin P was actually a mixture of two compounds, micrococcins P1 and P2, it was Bycroft and Gowland who assigned micrococcin P1 as structure 1 a. [23] (The proposal outlined in Ref.…”

Section: Introductionmentioning

confidence: 98%

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

2007

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Amino acids, the building blocks of proteins, also serve as precursors to a wide range of other naturally occurring substances including alkaloids, antibiotics, and, the subject of this Review, heterocyclic peptides. Simple alpha-amino acids are converted into complex arrays of heteroaromatic rings that display interesting and potent biological activity. The thiopeptide antibiotics, with their complex molecular architectures, are wonderful examples. In this Review we show how organic chemists have developed innovative methods for the synthesis of the heterocyclic ring systems, including routes inspired by the likely biosynthetic processes, and successfully assembled such building blocks into the final target molecule by application of orthogonal protecting groups and coupling methodologies.

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Total structure of the polythiazole-containing antibiotic micrococcin P. A 13C nuclear magnetic resonance study

Cited by 51 publications

References 0 publications

The Macrocyclic Peptide Antibiotic Micrococcin P₁Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese

The Macrocyclic Peptide Antibiotic Micrococcin P₁Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese

Total structure of the highly modified peptide antibiotic components of thiopeptin.

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

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Total structure of the polythiazole-containing antibiotic micrococcin P. A 13C nuclear magnetic resonance study

Cited by 51 publications

References 0 publications

The Macrocyclic Peptide Antibiotic Micrococcin P1Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese

The Macrocyclic Peptide Antibiotic Micrococcin P1Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese

Total structure of the highly modified peptide antibiotic components of thiopeptin.

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

Contact Info

Product

Resources

About

The Macrocyclic Peptide Antibiotic Micrococcin P₁Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese

The Macrocyclic Peptide Antibiotic Micrococcin P₁Is Secreted by the Food-Borne BacteriumStaphylococcus equorumWS 2733 and InhibitsListeria monocytogeneson Soft Cheese