Linked Life Data

11495926

Source:http://linkedlifedata.com/resource/pubmed/id/11495926

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2001-10-15
pubmed:databankReference
pubmed:abstractText
Balhimycin, a vancomycin-type antibiotic from Amycolatopsis mediterranei, contains the unusual amino acid (S)-3,5-dihydroxyphenylglycine (Dpg), with an acetate-derived carbon backbone. After sequence analysis of the biosynthetic gene cluster, one gene, dpgA, for a predicted polyketide synthase (PKS) was identified, sharing 20-30% identity with plant chalcone synthases. Inactivation of dpgA resulted in loss of balhimycin production, and restoration was achieved by supplementation with 3,5-dihydroxyphenylacetic acid, which is both a possible product of a PKS reaction and a likely precursor of Dpg. Enzyme assays with the protein expressed in Streptomyces lividans showed that this PKS uses only malonyl-CoA as substrate to synthesize 3,5-dihydroxyphenylacetic acid. The PKS gene is organized in an operon-like structure with three downstream genes that are similar to enoyl-CoA-hydratase genes and a dehydrogenase gene. The heterologous co-expression of all four genes led to accumulation of 3,5-dihydroxyphenylglyoxylic acid. Therefore, we now propose a reaction sequence. The final step in the pathway to Dpg is a transamination. A predicted transaminase gene was inactivated, resulting in abolished antibiotic production and accumulation of 3,5-dihydroxyphenylglyoxylic acid. Interestingly, restoration was only possible by simultaneous supplementation with (S)-3,5-dihydroxyphenylglycine and (S)-4-hydroxyphenylglycine, indicating that the transaminase is essential for the formation of both amino acids.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38370-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11495926-Amino Acids, pubmed-meshheading:11495926-Bacterial Proteins, pubmed-meshheading:11495926-Chromatography, High Pressure Liquid, pubmed-meshheading:11495926-Coenzyme A Ligases, pubmed-meshheading:11495926-Excitatory Amino Acid Antagonists, pubmed-meshheading:11495926-Gene Deletion, pubmed-meshheading:11495926-Glycine, pubmed-meshheading:11495926-Glycopeptides, pubmed-meshheading:11495926-Models, Chemical, pubmed-meshheading:11495926-Models, Genetic, pubmed-meshheading:11495926-Molecular Sequence Data, pubmed-meshheading:11495926-Multienzyme Complexes, pubmed-meshheading:11495926-Mutagenesis, Site-Directed, pubmed-meshheading:11495926-Plasmids, pubmed-meshheading:11495926-Resorcinols, pubmed-meshheading:11495926-Sequence Analysis, DNA, pubmed-meshheading:11495926-Streptomyces, pubmed-meshheading:11495926-Vancomycin
pubmed:year
2001
pubmed:articleTitle
A polyketide synthase in glycopeptide biosynthesis: the biosynthesis of the non-proteinogenic amino acid (S)-3,5-dihydroxyphenylglycine.
pubmed:affiliation
Universität Tübingen, Institut für Mikrobiologie and Biotechnologie, Auf der Morgenstelle, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't