Enzymatic Cascade to Evaluate the Tricyclization of Glycopeptide Antibiotic Precursor Peptides as a Prequel to Biosynthetic Redesign

Julien Tailhades; Yongwei Zhao; Melanie Schoppet; Anja Greule; Robert J. A. Goode; Ralf B. Schittenhelm; James J. De Voss; Max J. Cryle

doi:10.1021/acs.orglett.9b03245

Enzymatic Cascade to Evaluate the Tricyclization of Glycopeptide Antibiotic Precursor Peptides as a Prequel to Biosynthetic Redesign

Julien Tailhades, Yongwei Zhao, Melanie Schoppet, Anja Greule, Robert J. A. Goode, Ralf B. Schittenhelm, James J. De Voss, Max J. Cryle

Research output: Contribution to journal › Article › Research › peer-review

18 Citations (Scopus)

Abstract

Natural products are the greatest source of antimicrobial agents, although their structural complexity often renders synthetic production and diversification of key classes impractical. One pertinent example is the glycopeptide antibiotics (GPAs), which are highly challenging to synthesize due to their heavily cross-linked structures. Here, we report an optimized method that generates >75% tricyclic peptides from synthetic precursors in order to explore the acceptance of novel GPA precursor peptides by these key existent biosynthetic enzymes.

Original language	English
Pages (from-to)	8635-8640
Number of pages	6
Journal	Organic Letters
Volume	21
Issue number	21
DOIs	https://doi.org/10.1021/acs.orglett.9b03245
Publication status	Published - 1 Nov 2019

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10.1021/acs.orglett.9b03245

Cite this

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abstract = "Natural products are the greatest source of antimicrobial agents, although their structural complexity often renders synthetic production and diversification of key classes impractical. One pertinent example is the glycopeptide antibiotics (GPAs), which are highly challenging to synthesize due to their heavily cross-linked structures. Here, we report an optimized method that generates >75% tricyclic peptides from synthetic precursors in order to explore the acceptance of novel GPA precursor peptides by these key existent biosynthetic enzymes.",

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AU - Tailhades, Julien

AU - Zhao, Yongwei

AU - Schoppet, Melanie

AU - Greule, Anja

AU - Goode, Robert J. A.

AU - Schittenhelm, Ralf B.

AU - De Voss, James J.

AU - Cryle, Max J.

PY - 2019/11/1

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N2 - Natural products are the greatest source of antimicrobial agents, although their structural complexity often renders synthetic production and diversification of key classes impractical. One pertinent example is the glycopeptide antibiotics (GPAs), which are highly challenging to synthesize due to their heavily cross-linked structures. Here, we report an optimized method that generates >75% tricyclic peptides from synthetic precursors in order to explore the acceptance of novel GPA precursor peptides by these key existent biosynthetic enzymes.

AB - Natural products are the greatest source of antimicrobial agents, although their structural complexity often renders synthetic production and diversification of key classes impractical. One pertinent example is the glycopeptide antibiotics (GPAs), which are highly challenging to synthesize due to their heavily cross-linked structures. Here, we report an optimized method that generates >75% tricyclic peptides from synthetic precursors in order to explore the acceptance of novel GPA precursor peptides by these key existent biosynthetic enzymes.

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ER -

Enzymatic Cascade to Evaluate the Tricyclization of Glycopeptide Antibiotic Precursor Peptides as a Prequel to Biosynthetic Redesign

Abstract

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Other files and links

Improving on nature: diversifying glycopeptide antibiotics to kill the bacterial pathogen Staphylococcus aureus

Development of a bio-enabled synthesis for the Glycopeptide Antibiotics

Monash Proteomics & Metabolomics Facility

Cite this

Enzymatic Cascade to Evaluate the Tricyclization of Glycopeptide Antibiotic Precursor Peptides as a Prequel to Biosynthetic Redesign

Abstract

Access to Document

Other files and links

Projects

Improving on nature: diversifying glycopeptide antibiotics to kill the bacterial pathogen Staphylococcus aureus

Development of a bio-enabled synthesis for the Glycopeptide Antibiotics

Equipment

Monash Proteomics & Metabolomics Facility

Cite this