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

被引:88
作者
Borisova, Svetlana A. [1 ]
Circello, Benjamin T. [1 ,2 ]
Zhang, Jun Kai [2 ]
van der Donk, Wilfred A. [1 ,3 ,4 ]
Metcalf, William W. [1 ,2 ]
机构
[1] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA
[2] Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA
[3] Univ Illinois, Dept Chem, Urbana, IL 61801 USA
[4] Univ Illinois, Howard Hughes Med Inst, Urbana, IL 61801 USA
来源
CHEMISTRY & BIOLOGY | 2010年 / 17卷 / 01期
基金
美国国家卫生研究院;
关键词
AMINO-ACID LIGASE; THIAMIN PHOSPHATE SYNTHASE; D-ALANINE LIGASE; ESCHERICHIA-COLI; MACROPHOMATE SYNTHASE; PHOSPHINOTHRICIN TRIPEPTIDE; 3-DIMENSIONAL STRUCTURE; GLUTATHIONE SYNTHETASE; BIOTIN CARBOXYLASE; GENE-CLUSTER;
D O I
10.1016/j.chembiol.2009.11.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:28 / 37
页数:10
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