A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin.

A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Research Abstract Details 

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A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Abstract Text:

Penicillium decumbens is able to epoxidize cis-propenylphosphonic acid (cPA) to produce the antibiotic fosfomycin [FOM; also referred to as phosphonomycin and (-)-cis-1,2-epoxypropylphosphonic acid], a bioconversion of considerable commercial significance. We sought to improve the efficiency of the process by overexpression of the genes involved. A conventional approach of isolating the presumed epoxidase and its corresponding gene was not possible since cPA epoxidation could not be achieved with protein extracts. As an alternative approach, proteins induced by cPA were detected by two-dimensional gel electrophoresis. The observation that a 31-kDa protein (EpoA) was both cPA induced and overaccumulated in a strain which more efficiently converted cPA suggested that it might take part in the bioconversion. EpoA was purified, its amino acid sequence was partially determined, and the corresponding gene was isolated from cosmid and cDNA libraries with oligonucleotide probes. The DNA sequence for this gene (epoA) contained two introns and an open reading frame encoding a peptide of 277 amino acids having some similarity to oxygenases. When the gene was subcloned into P. decumbens, a fourfold increase in epoxidation activity was achieved. epoA-disruption mutants which were obtained by homologous recombination could not convert cPA to FOM. To investigate the regulation of the epoA promoter, the bialaphos resistance gene (bar, encoding phosphinothricin acetyltransferase) was used to replace the epoA-coding region. In P. decumbens, expression of the bar reporter gene was induced by cPA, FOM, and phosphorous acid but not by phosphoric acid.

A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Publishing Authors By Initials

For similar genetic processes: recombination, genetic: transformation, genetic research abstracts see: genetic processes: recombination, genetic: transformation, genetic research

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A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Applied and environmental microbiology

VOLUME: 65

Page Numbers: 1036-44

Journal Abbreviation: Appl. Environ. Microbiol.

ISSN: 0099-2240

DAY: 23

MONTH: Mar

YEAR: 1999

A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7605801

A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Keywords Mesh Terms:

KEYWORDS: Transformation, Genetic

MESH TERMS: metabolism

Chemical & Substance for Abstract: A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin. Information

Substance Name: epoxidase

Registry Number: EC 1.-

Grant and Affiliation Information for A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin.

AFFILIATION: Pharmaceutical Technology Laboratories, Meiji Seika Kaisha, Ltd., 788 Kayama, Odawara-shi 250, Japan.

Country: UNITED STATES

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MEDLINETA: Appl Environ Microbiol

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ACCESSION NUMBER: D73371

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