Biogenesis of the Unique 4 ',5 '-Dehydronucleoside of the Uridyl Peptide Antibiotic Pacidamycin

Amany E. Ragab; Sabine Grueschow; Daniel R. Tromans; Rebecca J. M. Goss

doi:10.1021/ja206163j

Biogenesis of the Unique 4 ',5 '-Dehydronucleoside of the Uridyl Peptide Antibiotic Pacidamycin

Amany E. Ragab, Sabine Grueschow, Daniel R. Tromans, Rebecca J. M. Goss^*

^*Corresponding author for this work

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

Abstract

The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.

Original language	English
Pages (from-to)	15288-15291
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	133
Issue number	39
DOIs	https://doi.org/10.1021/ja206163j
Publication status	Published - 5 Oct 2011

Keywords

NUCLEOSIDE ANTIBIOTICS
ENZYMES
GENE-CLUSTER
BIOSYNTHESIS
EVOLUTION

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10.1021/ja206163j

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title = "Biogenesis of the Unique 4 ',5 '-Dehydronucleoside of the Uridyl Peptide Antibiotic Pacidamycin",

abstract = "The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.",

keywords = "NUCLEOSIDE ANTIBIOTICS, ENZYMES, GENE-CLUSTER, BIOSYNTHESIS, EVOLUTION",

author = "Ragab, {Amany E.} and Sabine Grueschow and Tromans, {Daniel R.} and Goss, {Rebecca J. M.}",

year = "2011",

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doi = "10.1021/ja206163j",

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T1 - Biogenesis of the Unique 4 ',5 '-Dehydronucleoside of the Uridyl Peptide Antibiotic Pacidamycin

AU - Ragab, Amany E.

AU - Grueschow, Sabine

AU - Tromans, Daniel R.

AU - Goss, Rebecca J. M.

PY - 2011/10/5

Y1 - 2011/10/5

N2 - The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.

AB - The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.

KW - NUCLEOSIDE ANTIBIOTICS

KW - ENZYMES

KW - GENE-CLUSTER

KW - BIOSYNTHESIS

KW - EVOLUTION

U2 - 10.1021/ja206163j

DO - 10.1021/ja206163j

M3 - Article

SN - 0002-7863

VL - 133

SP - 15288

EP - 15291

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 39

ER -

Biogenesis of the Unique 4 ',5 '-Dehydronucleoside of the Uridyl Peptide Antibiotic Pacidamycin

Abstract

Keywords

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