Richard E. Moore

NAMING OF CYCLIC HEPTAPEPTIDE TOXINS OF CYANOBACTERIA (BLUE-GREEN-ALGAE)

UNIV ILLINOIS,COLL VET MED,URBANA,IL 61801; USA,MED RES INST INFECT DIS,DIV PATHOPHYSIOL,FREDERICK,MD 21701; UNIV NEW ENGLAND,DEPT BIOCHEM MICROBIOL & NUTR,ARMIDALE,NSW 2351,AUSTRALIA; UNIV ALBERTA,DEPT BOT,EDMONTON T6G 2E1,ALBERTA,CANADA; MEIJO UNIV,FAC PHARM,TEMPA KU,NAGOYA,AICHI 468,JAPAN; CHEM RES & DEV CTR,ABERDEEN,MD 21701; NATL BOT GARDENS,CLAREMENT,SOUTH AFRICA; ACAD SINICA,INST HYDROBIOL,WUHAN,PEOPLES R CHINA; NORWEGIAN INST WATER RES,OSLO 3,NORWAY; UNIV HAWAII MANOA,DEPT CHEM,HONOLULU,HI 96822; UNIV ILLINOIS,SCH CHEM SCI,URBANA,IL 61801; UNIV CALIF LOS ANGELES,DEPT MICROBIOL,LOS ANGELES,CA 90024; TOKYO METROPOLITAN RES LAB PUBL HLTH,SHINJUKU KU,TOKYO 160,JAPAN

Bioactive natural products from blue-green algae

Since 1981 we have cultured and prepared lipophilic and hydrophilic extracts from more than 1500 strains representing some 400 species of blue-green algae. Screening for a wide variety of potentially useful bioactivities, including cytotoxic, multi-drug-resistance reversal, antifungal, and antiviral effects, has led to the discovery and identification of numerous novel bioactive metabolites including peptides, macrolides and glycosides.A systematic evaluation of the chemical and environmental factors that influence the production of secondary metabolites inScytonema ocellatum, which produces tolytoxin (a macrocyclic lactone that depolymerizes actinin vivo to disrupt cell division in eukaryotic organisms), has shown that cyanophytes can be manipulated in culture to improve growth and product yields.

New apratoxins of marine cyanobacterial origin from guam and palau

Two collections of the marine cyanobacterium Lyngbya sp. from Guam and Palau that both afforded the potent cytotoxin apratoxin A (1) each yielded different structural analogues with lower degrees of methylation. The new apratoxins, termed apratoxins B (2) and C (3), were evaluated for their in vitro cytotoxicity along with semisynthetic E-dehydroapratoxin A (4) to identify key structural elements responsible for the cytotoxicity and to initiate SAR studies on this novel family of depsipeptides. All analogues 2-4 displayed weaker cytotoxicity than 1, but to different extents. While compound 3 closely approached the cytotoxicity of 1, compounds 2 and 4 exhibited significantly reduced activity, possibly also related to a conformational change. The 16S rRNA genes of the different apratoxin producers have partially been sequenced and compared, and other genetic differences are currently being revealed.

MsrB1 and MICALs Regulate Actin Assembly and Macrophage Function via Reversible Stereoselective Methionine Oxidation

Redox control of protein function involves oxidation and reduction of amino acid residues, but the mechanisms and regulators involved are insufficiently understood. Here, we report that in conjunction with Mical proteins, methionine-R-sulfoxide reductase B1 (MsrB1) regulates mammalian actin assembly via stereoselective methionine oxidation and reduction in a reversible, site-specific manner. Two methionine residues in actin are specifically converted to methionine-R-sulfoxide by Mical1 and Mical2 and reduced back to methionine by selenoprotein MsrB1, supporting actin disassembly and assembly, respectively. Macrophages utilize this redox control during cellular activation by stimulating MsrB1 expression and activity as a part of innate immunity. We identified the regulatory role of MsrB1 as a Mical antagonist in orchestrating actin dynamics and macrophage function. More generally, our study shows that proteins can be regulated by reversible site-specific methionine-R-sulfoxidation.

Sequence analysis and biochemical characterization of the nostopeptolide A biosynthetic gene cluster from Nostoc sp. GSV224

The cloning, sequencing, annotation and biochemical analysis of the nostopeptolide (nos) biosynthetic gene cluster from the terrestrial cyanobacterium Nostoc sp. GSV224 is described. Nostopeptolides A1 and A2 are cyclic peptide-polyketide hybrid natural products possessing nine amino acid residues, a butyric acid group, and an internal acetate-derived unit that are linked by peptide and ester bonds. The nos gene cluster includes eight ORFs encompassing 40 kb and includes most of the genes predicted to be involved in the biosynthesis and transport of this group of nonapeptolides. The genetic architecture and domain organization of the nos synthetase, a mixed non-ribosomal peptide synthetase-polyketide synthase, is co-linear in arrangement with respect to the putative order of the biosynthetic assembly of the lipopeptolide. Biochemical analysis of the NosA1, NosC1 and NosD1 adenylation domains coupled with the recent characterization of the nosE and nosF gene products, which are involved in the biosynthesis of the rare non-proteinogenic amino acid residue L-4-methylproline from L-leucine, support the involvement of this gene cluster in nostopeptolide biosynthesis.

Tjipanazoles, new antifungal agents from the blue-green alga Tolypothrix tjipanasensis

Abstract Bioactivity-directed isolation of the extract of the cyanophyte Tolypothrix tjipanasensis has led to the isolation of fifteen new N-glycosides of indolo[2,3-a]carbazoles designated tjipanazoles A1, A2, B, C1, C2, C3, C4, D, E, F1, F2, G1, G2, I and J. The structures of the alkaloids were determined by physical methods, chemical degradation and synthesis. Tjipanazole J is the only compound having the pyrrolo[3,4-c] ring of previously described indolo[2,3-a]carbazoles.

Toxins from cyanophytes belonging to the scytonemataceae

Two highly cytotoxic substances, scytophycins A and B, have been isolated from cultured Scitonema pseudohofmanni. Gross structures are proposed for scytophycins A and B, mostly on the basis of nuclear magnetic resonance spectral studies. The scytophycins are structurally related to tolytoxin, a toxic lipid found in field-collected Tolypothrix conglutinata var. colorata, another blue-green alga belonging to the family Scytonemataceae. At sublethal doses the scytophycins display moderate activity against P-388 lymphocytic leukemia and Lewis lung carcinoma in mice.

Electronic spectra of substituted naphthoquinones

Abstract Echinoderms elaborate many closely related structural pigments (spinochromes) based on a naphthoquinone skeleton. As an aid to structural elucidation of these compounds the electronic spectra of a large number of substituted naphthoquinones were examined. The bands in the 240–600 mμ region of the electronic spectra of 1,4-naphthoquinone, juglone, and naphthazarin have been assigned to either benzenoid or quinoid electronic excitations and the effect of substitution on the position of these bands has been systematically studied. As a result, a number of empirical correlations have been derived that are useful in the structure determination of unknown pigments.

ANTIVIRAL ACTIVITY OF CULTURED BLUE‐GREEN ALGAE (CYANOPHYTA)1

Lipophilic and hydrophilic extracts from approximately 600 strains of cultured cyanophytes, representing some 300 species, were examined for antiviral activity against three pathogenic viruses. Approximately 10% of the cultures produced substances that caused significant reduction in cytopathic effect normally associated with viral infection. The screening program identified the order Chroococcales as commonly producing antiviral agents.

Inhibitors of Ornithine Carbamoyltransferase from Pseudomonas syringae pv. phaseolicola. st]Revised Structure of Phaseolotoxin

Abstract The structure of phaseolotoxin, a toxin produced by cultured Pseudomonas syringae pv. phaseolicola , the causal agent of halo blight disease in bean plants is revised to 3. The structure of octicidin, isolated from leaves of bean plants infected with pv. phaseolicola . has been determined to be 4, a protease degradation product of 3 which is formed in the plant.