A New Anti-MRSA Antibiotic Complex, WAP-8294A. I. Taxonomy, Isolation and Biological Activities.

Kato, Azusa; Nakaya, Seigo; Kokubo, Naomi; Aiba, Yuji; Ohashi, Yoshitami; Hirata, Haruhisa; Fujii, Kiyonaga; Harada, Kenichi

doi:10.7164/antibiotics.51.929

Cited by 61 publications

(64 citation statements)

References 8 publications

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“…21 The antimicrobial activity of the minor components, WAP-8294A1, A4 and Ax13, were essentially same as that of the main one against Gram-positive bacteria including MRSA. 10 WAP-8294A2 shows a more potent activity against MRSA than the clinically useful anti-MRSA antibiotic, vancomycin. Particularly, these antibiotics have the characteristic advantage that the activity is highly enhanced by the addition of human serum.…”

Section: Discussionmentioning

confidence: 98%

“…10 Originally, the producing strain, Lysobacter sp., produces a WAP-8294 complex that contains at least 20 components. Of these components, the main one, WAP-8294A2, has been structurally characterized mainly by NMR techniques 11 and WAP-8294A1, A4 and Ax13 were isolated in a pure state by chromatographic techniques.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, these antibiotics have the characteristic advantage that the activity is highly enhanced by the addition of human serum. 10 Currently, the development of these compounds for clinical use is underway.…”

Section: Discussionmentioning

confidence: 99%

“…10 They are soluble in water, methanol and dimethyl-sulfoxide, and insoluble in acetone, ethyl acetate and chloroform. They are positive to the ninhydrin reaction.…”

Section: General Properties Of the Wap-8294a Componentsmentioning

confidence: 99%

“…8,9 We have also found a novel anti-MRSA antibiotic, WAP-8294A, that is a complex of 20 closely related components produced by Lysobacter sp. 10 The WAP-8294A2 (1) was isolated as the major component, while A1 (2), A4 (3) and Ax13 (4) were minor components. The major component of 1 showed a strong activity against Gram-positive bacteria including MRSA in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 95%

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A new anti-MRSA antibiotic complex, WAP-8294A II. Structure characterization of minor components by ESI LCMS and MS/MS

Kato

Hirata

Ohashi³

et al. 2011

J Antibiot

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The anti-MRSA antibiotic, WAP-8294A, was isolated from the fermentation broth of Lysobacter sp. The major component,and 2 mol of L-Ser, D-Orn and D-3-hydroxy-7-Me-octanoic acid. The structure of the WAP-8294A2 was mainly determined as a cyclic depsipeptide by 2D NMR experiments. However, it was difficult to use the NMR experiment to determine the minor components, A1, A4 and Ax13, isolated in small amounts. In the present study, ESI MS/MS was applied to the structure elucidation of these minor components. The structures of these minor components were determined on the basis of the fragmentation pattern of the product ions of WAP-8294A2 in the ESI MS/MS. As a result, it was confirmed that A1 and A4 had the same amino acid sequence as A2, while A1 and A4 had the 3-OH-octanoic acid and 3-OH-8-Me-nonanoic acid, respectively, in the place of the 3-OH-7-Meoctanoic acid in A2. In the structure of Ax13, it was found that Gly of A2 was changed to b-Ala of Ax13.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…10 They are soluble in water, methanol and dimethyl-sulfoxide, and insoluble in acetone, ethyl acetate and chloroform. They are positive to the ninhydrin reaction.…”

Section: General Properties Of the Wap-8294a Componentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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A new anti-MRSA antibiotic complex, WAP-8294A II. Structure characterization of minor components by ESI LCMS and MS/MS

Kato

Hirata

Ohashi³

et al. 2011

J Antibiot

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Molecular Editing Enhances Oxidation Resistance of Menaquinone‐Targeting Antibiotics Lysocin E and WAP‐8294A2

Nakata

Itoh

et al. 2023

Chemistry A European J

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Lysocin E (1 a) and WAP‐8294A2 (2 a) are peptidic natural products with 37‐ and 40‐membered macrocycles, respectively. Compounds 1 a and 2 a have potent antibacterial activities against Gram‐positive bacteria and share a unique mode of action. The electron‐rich indole ring of d‐Trp‐10 of 1 a and 2 a interacts with the electron‐deficient benzoquinone ring of menaquinone, which is a co‐enzyme in the bacterial respiratory chain. Formation of the electron‐donor‐acceptor complex causes membrane disruption, leading to cell death. Despite the promising activities of 1 a and 2 a, the susceptibility of Trp‐10 to oxidative degradation potentially deters the development of these compounds as antibacterial drugs. To address this issue, we replaced the indole ring with more oxidation‐resistant aromatics having a similar shape and electron‐rich character. Specifically, analogues with benzofuran (1 b/2 b), benzothiophene (1 c/2 c), and 1‐naphthalene (1 d/2 d) rings were designed, and chemically prepared by full solid‐phase total syntheses. Antibacterial assays of the six analogues revealed similar activities of 1 d/2 d and markedly reduced activities of 1 b/2 b and 1 c/2 c compared with 1 a/2 a. Equipotent 1 d and 2 d both showed high resistance to oxidation by peroxyl radicals. Hence, the present study demonstrates a new molecular editing strategy for conferring oxidation stability on natural products with pharmacologically useful functions.

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ChemInform Abstract: A New Anti‐MRSA Antibiotic Complex, WAP‐8294A. Part 1. Taxonomy, Isolation and Biological Activities.

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A New Anti-MRSA Antibiotic Complex, WAP-8294A. I. Taxonomy, Isolation and Biological Activities.

Cited by 61 publications

References 8 publications

A new anti-MRSA antibiotic complex, WAP-8294A II. Structure characterization of minor components by ESI LCMS and MS/MS

A new anti-MRSA antibiotic complex, WAP-8294A II. Structure characterization of minor components by ESI LCMS and MS/MS

Molecular Editing Enhances Oxidation Resistance of Menaquinone‐Targeting Antibiotics Lysocin E and WAP‐8294A2

ChemInform Abstract: A New Anti‐MRSA Antibiotic Complex, WAP‐8294A. Part 1. Taxonomy, Isolation and Biological Activities.

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