Discovery and Derivatization of Tridecaptin Antibiotics with Altered Host Specificity and Enhanced Bioactivity

Nataliia V. Machushynets; Karol Al Ayed; Barbara R. Terlouw; Chao Du; Ned P. Buijs; Joost Willemse; Somayah S. Elsayed; Julian Schill; Vincent Trebosc; Michel Pieren; Francesca M. Alexander; Stephen A. Cochrane; Mark R. Liles; Marnix H. Medema; Nathaniel I. Martin; Gilles P. van Wezel

doi:10.1021/acschembio.4c00034

Discovery and Derivatization of Tridecaptin Antibiotics with Altered Host Specificity and Enhanced Bioactivity

Nataliia V. Machushynets, Karol Al Ayed, Barbara R. Terlouw, Chao Du, Ned P. Buijs, Joost Willemse, Somayah S. Elsayed, Julian Schill, Vincent Trebosc, Michel Pieren, Francesca M. Alexander, Stephen A. Cochrane, Mark R. Liles, Marnix H. Medema, Nathaniel I. Martin, Gilles P. van Wezel^* (Co-auteur)

^*Bijbehorende auteur voor dit werk

NIOO - Microbial Ecology (ME)

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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The prevalence of multidrug-resistant (MDR) pathogens combined with a decline in antibiotic discovery presents a major challenge for health care. To refill the discovery pipeline, we need to find new ways to uncover new chemical entities. Here, we report the global genome mining-guided discovery of new lipopeptide antibiotics tridecaptin A₅ and tridecaptin D, which exhibit unusual bioactivities within their class. The change in the antibacterial spectrum of Oct-TriA₅ was explained solely by a Phe to Trp substitution as compared to Oct-TriA₁, while Oct-TriD contained 6 substitutions. Metabolomic analysis of producer Paenibacillus sp. JJ-21 validated the predicted amino acid sequence of tridecaptin A₅. Screening of tridecaptin analogues substituted at position 9 identified Oct-His9 as a potent congener with exceptional efficacy against Pseudomonas aeruginosa and reduced hemolytic and cytotoxic properties. Our work highlights the promise of tridecaptin analogues to combat MDR pathogens.

Originele taal-2	Engels
Artikelnummer	4c00034
Tijdschrift	ACS Chemical Biology
DOI's	https://doi.org/10.1021/acschembio.4c00034
Status	E-pub ahead of print - 11 apr. 2024

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10.1021/acschembio.4c00034Licentie: CC BY

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Machushynets, N. V., Al Ayed, K., Terlouw, B. R., Du, C., Buijs, N. P., Willemse, J., Elsayed, S. S., Schill, J., Trebosc, V., Pieren, M., Alexander, F. M., Cochrane, S. A., Liles, M. R., Medema, M. H., Martin, N. I., & van Wezel, G. P. (2024). Discovery and Derivatization of Tridecaptin Antibiotics with Altered Host Specificity and Enhanced Bioactivity. ACS Chemical Biology, Artikel 4c00034. Online publicatie vooraf. https://doi.org/10.1021/acschembio.4c00034

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title = "Discovery and Derivatization of Tridecaptin Antibiotics with Altered Host Specificity and Enhanced Bioactivity",

abstract = "The prevalence of multidrug-resistant (MDR) pathogens combined with a decline in antibiotic discovery presents a major challenge for health care. To refill the discovery pipeline, we need to find new ways to uncover new chemical entities. Here, we report the global genome mining-guided discovery of new lipopeptide antibiotics tridecaptin A5 and tridecaptin D, which exhibit unusual bioactivities within their class. The change in the antibacterial spectrum of Oct-TriA5 was explained solely by a Phe to Trp substitution as compared to Oct-TriA1, while Oct-TriD contained 6 substitutions. Metabolomic analysis of producer Paenibacillus sp. JJ-21 validated the predicted amino acid sequence of tridecaptin A5. Screening of tridecaptin analogues substituted at position 9 identified Oct-His9 as a potent congener with exceptional efficacy against Pseudomonas aeruginosa and reduced hemolytic and cytotoxic properties. Our work highlights the promise of tridecaptin analogues to combat MDR pathogens.",

author = "Machushynets, {Nataliia V.} and {Al Ayed}, Karol and Terlouw, {Barbara R.} and Chao Du and Buijs, {Ned P.} and Joost Willemse and Elsayed, {Somayah S.} and Julian Schill and Vincent Trebosc and Michel Pieren and Alexander, {Francesca M.} and Cochrane, {Stephen A.} and Liles, {Mark R.} and Medema, {Marnix H.} and Martin, {Nathaniel I.} and {van Wezel}, {Gilles P.}",

note = "Data archiving: not yet asked",

year = "2024",

month = apr,

day = "11",

doi = "10.1021/acschembio.4c00034",

language = "English",

journal = "ACS Chemical Biology",

issn = "1554-8929",

publisher = "American Chemical Society",

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Machushynets, NV, Al Ayed, K, Terlouw, BR, Du, C, Buijs, NP, Willemse, J, Elsayed, SS, Schill, J, Trebosc, V, Pieren, M, Alexander, FM, Cochrane, SA, Liles, MR, Medema, MH, Martin, NI & van Wezel, GP 2024, 'Discovery and Derivatization of Tridecaptin Antibiotics with Altered Host Specificity and Enhanced Bioactivity', ACS Chemical Biology. https://doi.org/10.1021/acschembio.4c00034

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T1 - Discovery and Derivatization of Tridecaptin Antibiotics with Altered Host Specificity and Enhanced Bioactivity

AU - Machushynets, Nataliia V.

AU - Al Ayed, Karol

AU - Terlouw, Barbara R.

AU - Du, Chao

AU - Buijs, Ned P.

AU - Willemse, Joost

AU - Elsayed, Somayah S.

AU - Schill, Julian

AU - Trebosc, Vincent

AU - Pieren, Michel

AU - Alexander, Francesca M.

AU - Cochrane, Stephen A.

AU - Liles, Mark R.

AU - Medema, Marnix H.

AU - Martin, Nathaniel I.

AU - van Wezel, Gilles P.

N1 - Data archiving: not yet asked

PY - 2024/4/11

Y1 - 2024/4/11

N2 - The prevalence of multidrug-resistant (MDR) pathogens combined with a decline in antibiotic discovery presents a major challenge for health care. To refill the discovery pipeline, we need to find new ways to uncover new chemical entities. Here, we report the global genome mining-guided discovery of new lipopeptide antibiotics tridecaptin A5 and tridecaptin D, which exhibit unusual bioactivities within their class. The change in the antibacterial spectrum of Oct-TriA5 was explained solely by a Phe to Trp substitution as compared to Oct-TriA1, while Oct-TriD contained 6 substitutions. Metabolomic analysis of producer Paenibacillus sp. JJ-21 validated the predicted amino acid sequence of tridecaptin A5. Screening of tridecaptin analogues substituted at position 9 identified Oct-His9 as a potent congener with exceptional efficacy against Pseudomonas aeruginosa and reduced hemolytic and cytotoxic properties. Our work highlights the promise of tridecaptin analogues to combat MDR pathogens.

AB - The prevalence of multidrug-resistant (MDR) pathogens combined with a decline in antibiotic discovery presents a major challenge for health care. To refill the discovery pipeline, we need to find new ways to uncover new chemical entities. Here, we report the global genome mining-guided discovery of new lipopeptide antibiotics tridecaptin A5 and tridecaptin D, which exhibit unusual bioactivities within their class. The change in the antibacterial spectrum of Oct-TriA5 was explained solely by a Phe to Trp substitution as compared to Oct-TriA1, while Oct-TriD contained 6 substitutions. Metabolomic analysis of producer Paenibacillus sp. JJ-21 validated the predicted amino acid sequence of tridecaptin A5. Screening of tridecaptin analogues substituted at position 9 identified Oct-His9 as a potent congener with exceptional efficacy against Pseudomonas aeruginosa and reduced hemolytic and cytotoxic properties. Our work highlights the promise of tridecaptin analogues to combat MDR pathogens.

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DO - 10.1021/acschembio.4c00034

M3 - Article

AN - SCOPUS:85190168323

SN - 1554-8929

JO - ACS Chemical Biology

JF - ACS Chemical Biology

M1 - 4c00034

ER -

Discovery and Derivatization of Tridecaptin Antibiotics with Altered Host Specificity and Enhanced Bioactivity

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