Biosynthesis of Rhizocticins, Antifungal Phosphonate Oligopeptides Produced by Bacillus subtilis ATCC6633

Svetlana A. Borisova; Benjamin T. Circello; Jun Kai Zhang; Wilfred A. van der Donk; William W. Metcalf

doi:10.1016/j.chembiol.2009.11.017

Biosynthesis of Rhizocticins, Antifungal Phosphonate Oligopeptides Produced by Bacillus subtilis ATCC6633

Svetlana A. Borisova, Benjamin T. Circello, Jun Kai Zhang, Wilfred A. van der Donk, William W. Metcalf

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

Abstract

Rhizocticins are phosphonate oligopeptide antibiotics containing the C-terminal nonproteinogenic amino acid (Z)-l-2-amino-5-phosphono-3-pentenoic acid (APPA). Here we report the identification and characterization of the rhizocticin biosynthetic gene cluster (rhi) in Bacillus subtilis ATCC6633. Rhizocticin B was heterologously produced in the nonproducer strain Bacillus subtilis 168. A biosynthetic pathway is proposed on the basis of bioinformatics analysis of the rhi genes. One of the steps during the biosynthesis of APPA is an unusual aldol reaction between phosphonoacetaldehyde and oxaloacetate catalyzed by an aldolase homolog RhiG. Recombinant RhiG was prepared, and the product of an in vitro enzymatic conversion was characterized. Access to this intermediate allows for biochemical characterization of subsequent steps in the pathway.

Original language	English (US)
Pages (from-to)	28-37
Number of pages	10
Journal	Chemistry and Biology
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.chembiol.2009.11.017
State	Published - Jan 29 2010

Keywords

CHEMBIO
MICROBIO

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2009.11.017

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title = "Biosynthesis of Rhizocticins, Antifungal Phosphonate Oligopeptides Produced by Bacillus subtilis ATCC6633",

abstract = "Rhizocticins are phosphonate oligopeptide antibiotics containing the C-terminal nonproteinogenic amino acid (Z)-l-2-amino-5-phosphono-3-pentenoic acid (APPA). Here we report the identification and characterization of the rhizocticin biosynthetic gene cluster (rhi) in Bacillus subtilis ATCC6633. Rhizocticin B was heterologously produced in the nonproducer strain Bacillus subtilis 168. A biosynthetic pathway is proposed on the basis of bioinformatics analysis of the rhi genes. One of the steps during the biosynthesis of APPA is an unusual aldol reaction between phosphonoacetaldehyde and oxaloacetate catalyzed by an aldolase homolog RhiG. Recombinant RhiG was prepared, and the product of an in vitro enzymatic conversion was characterized. Access to this intermediate allows for biochemical characterization of subsequent steps in the pathway.",

keywords = "CHEMBIO, MICROBIO",

author = "Borisova, {Svetlana A.} and Circello, {Benjamin T.} and Zhang, {Jun Kai} and {van der Donk}, {Wilfred A.} and Metcalf, {William W.}",

note = "Funding Information: We thank Feng Lin (Keck NMR laboratory, UIUC) for assistance with advanced NMR experiments, Lucas Li (Biotechnology Center, UIUC) for performing LC-MS analysis, and Nurul Zulkepli for help in preparation of pRhiG-C-His. This work was supported by the National Institutes of Health (GM PO1 GM077596). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH. ",

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AU - van der Donk, Wilfred A.

AU - Metcalf, William W.

N1 - Funding Information: We thank Feng Lin (Keck NMR laboratory, UIUC) for assistance with advanced NMR experiments, Lucas Li (Biotechnology Center, UIUC) for performing LC-MS analysis, and Nurul Zulkepli for help in preparation of pRhiG-C-His. This work was supported by the National Institutes of Health (GM PO1 GM077596). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH.

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N2 - Rhizocticins are phosphonate oligopeptide antibiotics containing the C-terminal nonproteinogenic amino acid (Z)-l-2-amino-5-phosphono-3-pentenoic acid (APPA). Here we report the identification and characterization of the rhizocticin biosynthetic gene cluster (rhi) in Bacillus subtilis ATCC6633. Rhizocticin B was heterologously produced in the nonproducer strain Bacillus subtilis 168. A biosynthetic pathway is proposed on the basis of bioinformatics analysis of the rhi genes. One of the steps during the biosynthesis of APPA is an unusual aldol reaction between phosphonoacetaldehyde and oxaloacetate catalyzed by an aldolase homolog RhiG. Recombinant RhiG was prepared, and the product of an in vitro enzymatic conversion was characterized. Access to this intermediate allows for biochemical characterization of subsequent steps in the pathway.

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Biosynthesis of Rhizocticins, Antifungal Phosphonate Oligopeptides Produced by Bacillus subtilis ATCC6633

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