Hamish McArthur - Academia.edu (original) (raw)

Papers by Hamish McArthur

Fems Microbiology Letters, Sep 1, 1995

The starter units for branched-chain and straight-chain fatty acid biosynthesis was investigated ... more The starter units for branched-chain and straight-chain fatty acid biosynthesis was investigated in vivo in three actinomycetes using stable isotopes. Branched-chain fatty acids, which constitute the majority of the fatty acid pool, were confirmed to be biosynthesized using the amino acid degradation products methylbutyryl-CoA and isobutyryl-CoA as starter units. Straight-chain fatty acids were shown to be constructed using butyryl-CoA as a starter unit. Isomerization of the valine catabolite isobutyryl-CoA was shown to be only a minor source of this butyryl-CoA.

Journal of Bacteriology, Mar 1, 1981

The main chain of teichoic acids can be assembled in cell-free membrane preparations by the trans... more The main chain of teichoic acids can be assembled in cell-free membrane preparations by the transfer of residues from the appropriate nucleotide precursors to an incompletely characterized amphiphilic molecule, lipoteichoic acid carrier (LTC). However, in the cell wall, the man chain is attached to peptidoglycan through a linkage unit which is synthesized independently. It is believed that, in these cell-free systems, lipid intermediates carrying linkage units are also able to accept residues directly from nucleotide precursors to build up the main chain. In this paper, we have shown that the main chain attached to LTC was transferred from LTC to lipids containing the linkage unit. Thus, in these systems, there appear to be two routes to the biosynthesis of teichoic acid-linkage unit complexes, one by direct assembly of the main chain on linkage unit lipids and the other by transfer of the preassembled main chain from LTC to the linkage unit. It was also shown that linkage unit lipids from different orgnisms were interchangeable and that these were used for polymer synthesis by BaciUus subtilis 3610, in which the teichoic acid is a poly(glycerol phosphate).

Journal of Bacteriology, Jun 1, 1995

A second cluster of genes encoding the E1 alpha, E1 beta, and E2 subunits of branched-chain alpha... more A second cluster of genes encoding the E1 alpha, E1 beta, and E2 subunits of branched-chain alpha-keto acid dehydrogenase (BCDH), bkdFGH, has been cloned and characterized from Streptomyces avermitilis, the soil microorganism which produces anthelmintic avermectins. Open reading frame 1 (ORF1) (bkdF, encoding E1 alpha), would encode a polypeptide of 44,394 Da (406 amino acids). The putative start codon of the incompletely sequenced ORF2 (bkdG, encoding E1 beta) is located 83 bp downstream from the end of ORF1. The deduced amino acid sequence of bkdF resembled the corresponding E1 alpha subunit of several prokaryotic and eukaryotic BCDH complexes. An S. avermitilis bkd mutant constructed by deletion of a genomic region comprising the 5' end of bkdF is also described. The mutant exhibited a typical Bkd- phenotype: it lacked E1 BCDH activity and had lost the ability to grow on solid minimal medium containing isoleucine, leucine, and valine as sole carbon sources. Since BCDH provides an alpha-branched-chain fatty acid starter unit, either S(+)-alpha-methylbutyryl coenzyme A or isobutyryl coenzyme A, which is essential to initiate the synthesis of the avermectin polyketide backbone in S. avermitilis, the disrupted mutant cannot make the natural avermectins in a medium lacking both S(+)-alpha-methylbutyrate and isobutyrate. Supplementation with either one of these compounds restores production of the corresponding natural avermectins, while supplementation of the medium with alternative fatty acids results in the formation of novel avermectins. These results verify that the BCDH-catalyzed reaction of branched-chain amino acid catabolism constitutes a crucial step to provide fatty acid precursors for antibiotic biosynthesis in S. avermitilis.

Infection and Immunity, 1986

An endogenous heparin-binding lectin activity isolated from rat lung was separated into two disti... more An endogenous heparin-binding lectin activity isolated from rat lung was separated into two distinct isolectin forms which showed subtle changes in carbohydrate specificity. The two lectin forms displayed different specificities toward alginic acid-purified cystic fibrosis isolates of Pseudomonas aeruginosa when assayed by inhibition of both hemagglutination and [3H]heparin binding. This ability of isolectin forms to show higher

Infection and Immunity, Nov 1, 1983

The specific interaction between the exopolysaccharide purified from a number of Pseudomonas aeru... more The specific interaction between the exopolysaccharide purified from a number of Pseudomonas aeruginosa isolates from cystic fibrosis patients and a rat lung heparin-lectin was assayed. The polysaccharide prepared from Homma serotypes M, B, I, and G did not act as hapten inhibitors of lectin activity, whereas the polymers prepared from ca. 80% of strains that did not type with Homma serum did act as hapten inhibitors. Inhibition was shown not to be due to lipopolysaccharide. The infrared spectrums of both inhibitory and noninhibitory polymers appeared very similar, although small amounts of glucose and an unidentified amino sugar were found only in the nontypable strains. This evidence suggests that rat lung lectin recognizes and distinguishes a specific type of alginate-like polymer prevalant on the Homma nontypable P. aeruginosa.

Journal of Bacteriology, Jun 1, 1997

A stable-isotope assay was used to analyze the effectiveness of various perdeuterated short-chain... more A stable-isotope assay was used to analyze the effectiveness of various perdeuterated short-chain acyl coenzyme A (acyl-CoA) compounds as starter units for straight-and branched-chain fatty acid biosynthesis in cell extracts of Streptomyces collinus. In these extracts perdeuterated isobutyryl-CoA was converted to isopalmitate (a branched-chain fatty acid), while butyryl-CoA was converted to palmitate (a straight-chain fatty acid). These observations are consistent with previous in vivo analyses of fatty acid biosynthesis in S. collinus, which suggested that butyryl-CoA and isobutyryl-CoA function as starter units for palmitate and isopalmitate biosynthesis, respectively. Additionally, in vitro analysis demonstrated that acetyl-CoA can function as a starter unit for palmitate biosynthesis. Palmitate biosynthesis and isopalmitate biosynthesis in these cell extracts were both effectively inhibited by thiolactomycin, a known type II fatty acid synthase inhibitor. In vivo experiments demonstrated that concentrations of thiolactomycin ranging from 0.1 to 0.2 mg/ml produced both a dramatic decrease in the cellular levels of branched-chain fatty acids and a surprising three-to fivefold increase in the cellular levels of the straight-chain fatty acids palmitate and myristate. Additional in vivo incorporation studies with perdeuterated butyrate suggested that, in accord with the in vitro studies, the biosynthesis of the palmitate from butyryl-CoA decreases in the presence of thiolactomycin. In contrast, in vivo incorporation studies with perdeuterated acetate demonstrated that the biosynthesis of palmitate from acetyl-CoA increases in the presence of thiolactomycin. These observations clearly demonstrate that isobutyryl-CoA is a starter unit for isopalmitate biosynthesis and that either acetyl-CoA or butyryl-CoA can be a starter unit for palmitate biosynthesis in S. collinus. However, the pathway for palmitate biosynthesis from acetyl-CoA is less sensitive to thiolactomycin, and it is suggested that the basis for this difference is in the initiation step.

Bioorganic Chemistry, Mar 1, 1980

Abstract Membranes from Micrococcus varians catalyse the de novo synthesis of poly(N-acetylglucos... more Abstract Membranes from Micrococcus varians catalyse the de novo synthesis of poly(N-acetylglucosamine 1-phosphate) attached to noncrosslinked peptidoglycan through a linkage unit of N-acetylglucosamine phosphate-tri(glycerol phosphate). The absence of CDP-glycerol, one of the precursors of linkage unit, precludes the attachment of the sugar 1-phosphate polymer. This report is the first of such polymer attachment performed by membranes which are completely free of cell walls.

Journal of Organic Chemistry, Nov 1, 1998

L'invention concerne des composes de la formule (1) et des sels pharmaceutiquement acceptable... more L'invention concerne des composes de la formule (1) et des sels pharmaceutiquement acceptables, des promedicaments et des solvats desdits composes. Dans ladite formule, R?1, R2, R3, R4, R5, R17, Rf?, A, X, et Y sont tels que definis dans le memorandum descriptif. L'invention concerne en outre des compositions pharmaceutiques contenant les composes de la formule (1), des methodes d'utilisation des composes de la formule (1) pour traiter des infections, et des methodes de preparation des composes de la formule (1).

European Journal of Medicinal Chemistry, 2002

who sent to the Gif laboratory charcoals collected in the vicinity of the skeleton for radiocarbo... more who sent to the Gif laboratory charcoals collected in the vicinity of the skeleton for radiocarbon dating. Twenty-nine charcoal samples were dated from different levels of the stratigraphy of the cave (Délibrias et al. 1986). Recently, new charcoal samples were discovered within Laming-Emperaire's correspondence and were subsequently dated by the Saclay AMS laboratory. The new results confirm the age of Luzia; however, the ages correspond to the younger part of the interval: charcoals found near Luzia's skull give an age of 10,030 ± 60 14 C yr BP (11,243-11,710 cal BP).

A second cluster of genes encoding the E1a, E1b, and E2 subunits of branched-chain a-keto acid de... more A second cluster of genes encoding the E1a, E1b, and E2 subunits of branched-chain a-keto acid dehydro-genase (BCDH), bkdFGH, has been cloned and characterized from Streptomyces avermitilis, the soil microor-ganism which produces anthelmintic avermectins. Open reading frame 1 (ORF1) (bkdF, encoding E1a), would encode a polypeptide of 44,394 Da (406 amino acids). The putative start codon of the incompletely sequenced ORF2 (bkdG, encoding E1b) is located 83 bp downstream from the end of ORF1. The deduced amino acid sequence of bkdF resembled the corresponding E1a subunit of several prokaryotic and eukaryotic BCDH complexes. An S. avermitilis bkd mutant constructed by deletion of a genomic region comprising the 5 * end of bkdF is also described. The mutant exhibited a typical Bkd2 phenotype: it lacked E1 BCDH activity and had lost the ability to grow on solid minimal medium containing isoleucine, leucine, and valine as sole carbon sources. Since BCDH provides an a-branched-chain fatty ...

Journal of Industrial Microbiology & Biotechnology, 2001

The biosynthesis of complex reduced polyketides is catalysed in actinomycetes by large multifun... more The biosynthesis of complex reduced polyketides is catalysed in actinomycetes by large multifunctional enzymes, the modular Type I polyketide synthases (PKSs). Most of our current knowledge of such systems stems from the study of a restricted number of macrolide-synthesising enzymes. The sequencing of the genes for the biosynthesis of monensin A, a typical polyether ionophore polyketide, provided the first genetic

FEMS Microbiology Letters, 1981

British Polymer Journal

... Hamish A. 1. McArthur ... Poly(ribito1 phosphate) synthesis can occur from CDP-ribitol alone;... more ... Hamish A. 1. McArthur ... Poly(ribito1 phosphate) synthesis can occur from CDP-ribitol alone; no ribitol-containing lipids are formed, UDP-GlcNAc and CDP-glycerol, the linkage unit precursors, have no effect when added singly, but when present together produce a large ...