Investigating β-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins

Brad Haltli; Ying Tan; Nathan A. Magarvey; Melissa Wagenaar; Xihou Yin; Michael Greenstein; John A. Hucul; T. Mark Zabriskie

doi:10.1016/j.chembiol.2005.09.013

Investigating β-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins

Brad Haltli, Ying Tan, Nathan A. Magarvey, Melissa Wagenaar, Xihou Yin, Michael Greenstein, John A. Hucul, T. Mark Zabriskie

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

44 Scopus citations

Abstract

The mannopeptimycins (MPPs) are potent glycopeptide antibiotics that contain both D and L forms of the unique, arginine-derived amino acid β-hydroxyenduracididine (βhEnd). The product of the mppO gene in the MPP biosynthetic cluster resembles several non-heme iron, α-ketoglutarate- dependent oxygenases, such as VioC and clavaminate synthase. The role of MppO in βhEnd biosynthesis was confirmed through inactivation of mppO, which yielded a strain that produced dideoxy-MPPs, indicating that mppO is essential for generating the β-hydroxy functionality for both βhEnd residues. Characterization in vitro of recombinant His₆-MppO expressed in E. coli revealed that MppO selectively hydroxylates the β carbon of free L-enduracididine.

Original language	English (US)
Pages (from-to)	1163-1168
Number of pages	6
Journal	Chemistry and Biology
Volume	12
Issue number	11
DOIs	https://doi.org/10.1016/j.chembiol.2005.09.013
State	Published - Nov 2005
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

Access to Document

10.1016/j.chembiol.2005.09.013

Cite this

@article{dbf06a3068564b71b6448974a69f9a44,

title = "Investigating β-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins",

abstract = "The mannopeptimycins (MPPs) are potent glycopeptide antibiotics that contain both D and L forms of the unique, arginine-derived amino acid β-hydroxyenduracididine (βhEnd). The product of the mppO gene in the MPP biosynthetic cluster resembles several non-heme iron, α-ketoglutarate- dependent oxygenases, such as VioC and clavaminate synthase. The role of MppO in βhEnd biosynthesis was confirmed through inactivation of mppO, which yielded a strain that produced dideoxy-MPPs, indicating that mppO is essential for generating the β-hydroxy functionality for both βhEnd residues. Characterization in vitro of recombinant His6-MppO expressed in E. coli revealed that MppO selectively hydroxylates the β carbon of free L-enduracididine.",

author = "Brad Haltli and Ying Tan and Magarvey, {Nathan A.} and Melissa Wagenaar and Xihou Yin and Michael Greenstein and Hucul, {John A.} and Zabriskie, {T. Mark}",

note = "Funding Information: This work was supported in part by the National Institutes of Health (grant GM69320 to T.M.Z.). We thank Quan Zhang for technical assistance, Dr. Edmund Graziani for providing D,L-End samples, Dr. Jason Lotvin for providing S. hygroscopicus strains NRRL 30450 and NRRL 30443, and Dr. Xidong Feng for conducting the high-resolution FTMS analysis. ",

year = "2005",

month = nov,

doi = "10.1016/j.chembiol.2005.09.013",

language = "English (US)",

volume = "12",

pages = "1163--1168",

journal = "Chemistry and Biology",

issn = "1074-5521",

publisher = "Elsevier Inc.",

number = "11",

}

TY - JOUR

T1 - Investigating β-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins

AU - Haltli, Brad

AU - Tan, Ying

AU - Magarvey, Nathan A.

AU - Wagenaar, Melissa

AU - Yin, Xihou

AU - Greenstein, Michael

AU - Hucul, John A.

AU - Zabriskie, T. Mark

N1 - Funding Information: This work was supported in part by the National Institutes of Health (grant GM69320 to T.M.Z.). We thank Quan Zhang for technical assistance, Dr. Edmund Graziani for providing D,L-End samples, Dr. Jason Lotvin for providing S. hygroscopicus strains NRRL 30450 and NRRL 30443, and Dr. Xidong Feng for conducting the high-resolution FTMS analysis.

PY - 2005/11

Y1 - 2005/11

N2 - The mannopeptimycins (MPPs) are potent glycopeptide antibiotics that contain both D and L forms of the unique, arginine-derived amino acid β-hydroxyenduracididine (βhEnd). The product of the mppO gene in the MPP biosynthetic cluster resembles several non-heme iron, α-ketoglutarate- dependent oxygenases, such as VioC and clavaminate synthase. The role of MppO in βhEnd biosynthesis was confirmed through inactivation of mppO, which yielded a strain that produced dideoxy-MPPs, indicating that mppO is essential for generating the β-hydroxy functionality for both βhEnd residues. Characterization in vitro of recombinant His6-MppO expressed in E. coli revealed that MppO selectively hydroxylates the β carbon of free L-enduracididine.

AB - The mannopeptimycins (MPPs) are potent glycopeptide antibiotics that contain both D and L forms of the unique, arginine-derived amino acid β-hydroxyenduracididine (βhEnd). The product of the mppO gene in the MPP biosynthetic cluster resembles several non-heme iron, α-ketoglutarate- dependent oxygenases, such as VioC and clavaminate synthase. The role of MppO in βhEnd biosynthesis was confirmed through inactivation of mppO, which yielded a strain that produced dideoxy-MPPs, indicating that mppO is essential for generating the β-hydroxy functionality for both βhEnd residues. Characterization in vitro of recombinant His6-MppO expressed in E. coli revealed that MppO selectively hydroxylates the β carbon of free L-enduracididine.

UR - http://www.scopus.com/inward/record.url?scp=27744534400&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744534400&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2005.09.013

DO - 10.1016/j.chembiol.2005.09.013

M3 - Article

C2 - 16298295

AN - SCOPUS:27744534400

SN - 1074-5521

VL - 12

SP - 1163

EP - 1168

JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 11

ER -

Investigating β-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this