Biomedical subjects

Cormac D Murphy

Publications and source records attributed to Cormac D Murphy.

6 recordsLinked to original sources

PubMed2006

Biosynthetic origin of [R-(Z)]-4-amino-3-chloro-2-pentenedioic acid in Streptomyces viridogenes.

The biosynthesis of the chlorinated amino acid [R-(Z)]-4-amino-3-chloro-2-pentenedioic acid (ACPA) was investigated. Feeding studies with Streptomyces viridogenes were conducted in resting cells. Substantial incorporation from [(15)N]- and [(13)C]-enriched glutamate and proline indicated that the biosynthetic origin of ACPA is one of these amino acids. Experiments with deuterated glutamate and proline imply that chlorination does not occur via a radical mechanism, but rather suggest that a FADH(2)-dependent halogenase is involved.

Glutamates↗

PubMed2006

Fluorophenol oxidation by a fungal chloroperoxidase.

Caldariomyces fumago chloroperoxidase degrades monofluorophenols at both pH 3 and pH 6. 4-Fluorophenol is most readily degraded and its oxidation is most efficient at pH 6. GC-MS analyses of the reaction products revealed compounds relating to the reaction of fluorophenol radical. The degradation of fluorinated compounds is of significant environmental interest and this versatile enzyme may by employed to treat contaminated soil or water prior to discharge.

Ascomycota↗

PubMed2006

Recent developments in enzymatic chlorination.

While the existence of chlorinated natural products has been known for over 100 years, our understanding of the enzymology of biological chlorination reactions has been limited to chloroperoxidases, which are now known not to play a significant role in chlorometabolite biosynthesis. The discoveries of new classes of halogenases, described in this Highlight, have shed new light on the mechanisms of enzymatic chlorination of aromatic and aliphatic compounds.

Biological Products↗

PubMed2004

A 19F NMR study of fluorobenzoate biodegradation by Sphingomonas sp. HB-1.

While several microorganisms readily degrade 2- and 4-fluorobenzoates, only a very small number appear to catabolise the 3-fluoro isomer, owing to the accumulation of toxic intermediates. Here we describe the isolation of a bacterium capable of using 3-fluorobenzoate as a sole source of carbon and energy, and the experiments conducted to define the steps involved in the biodegradation of this compound. The organism was identified as a strain belonging to the genus Sphingomonas by sequence analysis of its 16S rRNA gene. To date no other organism from this genus is known to degrade this compound. Using fluorine nuclear magnetic resonance spectroscopy (19F NMR) to analyse the culture supernatant it was possible to observe the disappearance of 3-fluorobenzoate and the appearance of fluoride ion and four other fluorinated compounds. These were identified as 3-fluorocatechol, 2-fluoromuconic acid and 3- and 5-fluoro-1,2-dihydro-1,2-dihydroxybenzoates. Thus, the likely catabolic pathway involves dioxygenation of 3-fluorobenzoate yielding fluorocatechol and subsequent intra-diol cleavage to yield fluoromuconic acid. The organism can also use 2- and 4-fluorobenzoates as growth substrates.

Benzoates↗

PubMed2003

Fluorinated natural products: the biosynthesis of fluoroacetate and 4-fluorothreonine in Streptomyces cattleya.

Organofluorine compounds are rare in Nature, with only a handful known to be produced by some species of plant and two microorganisms. Consequently, the mechanism of enzymatic carbon-fluorine bond formation is poorly understood. The bacterium Streptomyces cattleya biosynthesises fluoroacetate and 4-fluorothreonine as secondary metabolites and is a convenient system to study the biosynthesis and enzymology of fluorometabolite production. Using stable-isotope labelled precursors it has been shown that there is a common intermediate in the biosynthesis of the fluorometabolites, which has recently been identified as fluoroacetaldehyde. Studies with cell-free extracts of S. cattleya have identified two enzymes, an aldehyde dehydrogenase and a threonine transaldolase, that are involved in the biotransformation of fluoroacetaldehyde to fluoroacetate and 4-fluorothreonine.

Acetaldehyde↗

PubMed2002

Biochemistry: biosynthesis of an organofluorine molecule.

Although fluorine in the form of fluoride minerals is the most abundant halogen in the Earth's crust, only 12 naturally occurring organofluorine compounds have so far been found, and how these are biosynthesized remains a mystery. Here we describe an enzymatic reaction that occurs in the bacterium Streptomyces cattleya and which catalyses the conversion of fluoride ion and S-adenosylmethionine (SAM) to 5'-fluoro-5'-deoxyfluoroadenosine (5'-FDA). To our knowledge, this is the first fluorinase enzyme to be identified, a discovery that opens up a new biotechnological opportunity for the preparation of organofluorine compounds.

Catalysis↗