Studies on new antimetabolite produced by microorganism. III. Structure of plumbemycin A and B, antagonists of L-threonine from Streptomyces plumbeus.

Park, Boo Kil; Hirota, Akira; Sakai, Heiichi

doi:10.1271/bbb1961.41.573

Cited by 26 publications

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“…The following years brought the discovery of a family of antibiotics called rhizocticins (compounds 33-36) [80,81], plumbemycins (compounds 37 and 38) [81][82][83], and phosacetamycin (compound 39) [84], first isolated as secondary metabolites of Bacillus subtilis on the basis of their antifungal activity and were later found as products of Streptomyces plumbeus. They form a library of di-and tripeptides containing C-terminal (Z)-L-2-amino-5-phosphono-3-pentenoic acid, a mimetic of phosphonothreonine, which is the substrate for threonine synthetase.…”

Section: Phosphonopeptide Antibioticsmentioning

confidence: 99%

Phosphonates: Their Natural Occurrence and Physiological Role

Kafarski¹

2020

Contemporary Topics About Phosphorus in Biology and Materials

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The first natural compound containing carbon-to-phosphorus bond-ciliatine was discovered 60 years ago, and for four decades, phosphonates were considered simply as a biological curiosity. Finding the importance of these compounds in biogeochemical phosphorus cycling, their role in methane production, as well as discovery of numerous phosphonates and phosphonopeptides of promising antibacterial and antifungal activities has stimulated the development of studies on this class of compounds, especially on their metabolism and biochemistry. These studies are driven by the use of 31 P NMR and by a clever combination of genomics and innovative chemistry by using the method of selective labeling of metabolites. These studies revealed unusual and interesting chemistry of these compounds.

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Section: Phosphonopeptide Antibioticsmentioning

confidence: 99%

Phosphonates: Their Natural Occurrence and Physiological Role

Kafarski¹

2020

Contemporary Topics About Phosphorus in Biology and Materials

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“…As mentioned for PTT, the peptidic phosphonate antibiotics promote uptake by the target organism(s). Upon translocation, these peptides are hydrolyzed to release the active phosphonate-containing amino acids (129-133). Hydrolysis of the C -terminal peptide linkage of dehydrophos would result in an enamine that is expected to hydrolyze to methyl acetylphosphonate, which is a structural analog of pyruvate and could inhibit pyruvate utilizing enzymes.…”

Section: Dehydrophosmentioning

confidence: 99%

Biosynthesis of Phosphonic and Phosphinic Acid Natural Products

Metcalf

Donk

2009

Annu. Rev. Biochem.

307

299

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Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. Recent years have seen a renewed interest in the biochemistry and biology of these compounds with the cloning of the biosynthetic gene clusters for several family members. This review discusses the commonalities and differences in the molecular logic that lies behind the biosynthesis of these compounds. The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin, and the clinical candidate for treatment of malaria FR900098, is presented. Many of the enzymes involved in the biosynthesis of these compounds catalyze chemically and biologically unprecedented transformations and a wealth of new biochemistry has been revealed through their study. These studies have also suggested new strategies for natural product discovery. metcalf@uiuc.edu, vddonk@uiuc.edu. Summary Points •Phosphonates and phosphinates function by mimicking phosphate esters or anhydrides or carboxylate groups in enzyme substrates. As such, a large number of enzymes can be potential targets of this class of compounds.• The number of unprecedented reactions involved in the biosynthesis of fosfomycin, phosphinothricin, and FR900098 is an indication of the wealth of novel biochemistry used in the biosynthesis of this class of compounds.• Phosphoenolpyruvate (PEP) mutase catalyzes the C-P bond-forming step in all naturally occurring phosphonates for which the gene clusters are currently known. Hence, degenerate primers for PEPM can be used for the discovery of new phosphonate encoding gene clusters and hence new natural products.• Given the current commercial use of phosphonates and phosphinates in medicine and agriculture, discovery of new naturally occurring compounds beyond the twenty or so currently known structures may provide an important untapped source of new products for human use. Future issues• Based on the large number of metabolic processes that can be targeted with phosphonates, numerous phosphonate and phosphinate containing natural products likely remain to be discovered. Future studies will confirm or refute this hypothesis.• The fundamentally new radical-SAM strategy for methylation of unactivated carbon centers must be confirmed or disproven by in vitro studies.• The molecular logic that dictates epoxidation by HppE and C-C bond cleavage in HEPD is not understood and requires further investigation. Fine-tuning the activities of these enzymes may result in useful catalysts for synthetic purposes.• What is the cellular target of dehydrophos?• What alternative strategies are used in Nature to install a C-P bond that do not rely on the PEP mutase-like reaction?

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“…A direct P-CH 2 bond was evidenced by triplet splitting ( J =21.2 Hz) in the 1 H-coupled 31 P NMR spectrum and by the large coupling constant of J =128.3 Hz in the 13 C NMR spectrum for a CH 2 signal at 28.5 ppm. The structure of phosacetamycin was found to be analogous to 2-amino-5-phosphono-3-pentenoic acid (APPA), a constituent of the rhizocticins (rhizocticin A, Gly-APPA; rhizocticin B, Val-Gly-APPA; rhizocticin C, Ile-Gly-APPA; rhizocticin D, Leu-Gly-APPA) (21) and plumbemycins (plumbemycin A, Ala-Asp-APPA; plumbemycin B Ala-Asn-APPA) (22), by 1 H- 1 H COSY correlations of H-1 with H-2, H-3 with H-2 and H-4, 1 H- 1 H TOCSY correlations of H-1, H-2, H-3, and H-4, and 1 H- 13 C HMBC correlations of H-4 with C-5. APPA and phosacetamycin differ in that phosacetamycin possesses an acetamide group, which has additional signals corresponding to C-1′ (δc 173.1) and C-2′ (δc 21.8) and 1 H- 13 C HMBC correlations of C-1′ with H-4 and H-2′.…”

Section: Resultsmentioning

confidence: 99%

Discovery of the Antibiotic Phosacetamycin via a New Mass Spectrometry-Based Method for Phosphonic Acid Detection

Evans¹,

Zhao²,

Gao³

et al. 2013

ACS Chem. Biol.

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Naturally occurring phosphonates such as phosphinothricin (Glufosinate, a commercially used herbicide) and fosfomycin (Monurol, a clinically used antibiotic) have proved to be potent and useful biocides. Yet this class of natural products is still an under explored family of secondary metabolites. Discovery of the biosynthetic pathways responsible for the production of these compounds has been simplified by using gene based screening approaches, but detection and identification of the natural products the genes produce has been hampered by a lack of high-throughput methods for screening potential producers under various culture conditions. Here we present an efficient mass-spectrometric method for the selective detection of natural products containing phosphonate and phosphinate functional groups. We have used this method to identify a new phosphonate metabolite, phosacetamycin, whose structure, biological activity, and biosynthetic gene cluster are reported.

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Studies on new antimetabolite produced by microorganism. III. Structure of plumbemycin A and B, antagonists of L-threonine from Streptomyces plumbeus.

Abstract: The structure of plumbemycin A and B, new antimetabolites from Streptomyces plumbeus , which are antagonist of L-threonine, were assigned to be L-alanyl-L-aspartyl-D-2-amino-5phosphono-3-cis-pentenoic acid and L-alanyl-L-asparaginyl-D-2-amino-5-phosphono-3-cispentenoic acid, respectively.

Cited by 26 publications

References 0 publications

Phosphonates: Their Natural Occurrence and Physiological Role

Phosphonates: Their Natural Occurrence and Physiological Role

Biosynthesis of Phosphonic and Phosphinic Acid Natural Products

Discovery of the Antibiotic Phosacetamycin via a New Mass Spectrometry-Based Method for Phosphonic Acid Detection

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