Tapping uncultured microorganisms through metagenomics for drug discovery

Natural products have been an important historical source of therapeutic agents. Microorganisms are major source of bioactive natural products, and several microbial products including antibiotics, anti-inflammatory, anti-tumour, immunosuppressants and others are currently used as therapeutic agents for human and  domestic animals. Most of these products were obtained from cultured environmental microorganisms. However, it is widely accepted that a very large majority of the microorganisms present in natural  environments are not readily cultured under laboratory conditions, and therefore are not accessible for drug  discovery. Metagenomics is a recent culture-independent approach that has been developed to access the  collective genomes of natural bacterial populations. It enables discovery of the diverse biosynthetic pathways encoded by diverse microbial assemblages that are known to be present in the environment but not-yet  cultured. Recently, several new bioactive molecules and proteins have been discovered using a metagenomic approach. This review highlights the recent methodologies, limitations, and applications of metagenomics for the discovery of new drugs. Moreover, it shows how a multidisciplinary approach combining metagenomics with other technologies can expedite and revolutionize drug discovery from diverse environmental microorganisms.Key words: Microbial diversity, metagenomics, natural products, drug discovery, microbial ecology

PROTECTIVE EFFECT OF L-CARNITINE AND BAKER YEAST SACCHAROMYCES CEREVISIAE AGAINST HEPATIC TOXICITY INDUCED BY VALPROATE AS ANTIEPILEPTIC DRUG IN RATS

Objective: The aim of this work was to investigate the protective role of L-carnitine and baker yeast (Saccharomyces cerevisiae) against the effect of sodium valproate (VPA) induced toxicity and oxidative stress in the liver.Methods: Chronic administration of sodium valproate was studied by oral administration of VPA for six months. The protective effect was conducted by an administration of L-carnitine or/and baker yeast for one month before chronic administration of VPA. Some biochemical parameters, lipid profile, oxidative stress and histopathological studies were analyzed.Results: Chronic administration of VPA for six months caused a significant increase in serum amino transferases (AST, ALT), alkaline phosphatase (ALP), bilirubin, total lipids, total cholesterol, low density lipoprotein (LDL) as well as oxidative stress; malodialdehyde (MDA) and nitric oxide. While decreased total protein, albumin, and globulin in addition to glutathione peroxidase and superoxide dismutase (SOD). The administration of L-carnitine and baker yeast cause significant decreases in the activities of AST, ALT, bilirubin, lipid peroxidation, LDL level and MDA levels and return the levels of total protein, albumin, globulin, glutathione peroxidase and SOD to the normal levels. Histopathological results revealed improvement of the liver structure.Conclusion: L-carnitine and baker yeast (Saccharomyces cerevisiae) offer protection to the liver by preserving the structural integrity of hepatocellular membrane against sodium valproate induced hepatotoxicity and oxidative stress.Â

Notes on the Nesting Biology of the Small Carpenter Bee Ceratina smaragdula (Hymenoptera: Apidae) in Northwestern Pakistan

The nesting biology and some foraging activities of the familiar, brilliant metallic green, small carpenter bee Ceratina (Pithitis) smaragdula (F.) (Hymenoptera: Apidae) is documented from the northwestern-most extent of its natural distribution, as the species is a potentially important pollinator of leguminous and cucurbit crops in the region. Numerous nests around the village of Ismaila, Swabi, Khyber Pakhtunkhwa Province, Pakistan, were observed and sampled from Jun through Aug 2012. Nest details were recorded and foraging times on various floral species were documented, with bees preferentially nesting in wooden stalks of Ravenna grass (Saccharum ravennae L.; Poales: Poaceae), life cycles lasting 28 to 32 d, and conditions offering the potential for easy management. The importance of such studies on wild bees in Pakistan is stressed, as are the development of biotic surveys on bees and the training of regional melittologists, coupled with outreach activities. Resumen La biología de la anidación y algunas actividades de forrajeo de la pequeña abeja carpintera Ceratina (Pithitis) smaragdula (F.) (Hymenoptera: Apidae) de tipo familiar y brillante color verde metálico está documentado desde el punto mas noroeste de su distribución natural, ya que la especie es potencialmente un importante polinizador de legumbres y cucurbitáceas en la región. Se observaron numerosos nidos alrededor del pueblo de Ismaila, Swabi, Khyber Pakhtunkhwa Provincia, Pakistán, y se tomaron muestras desde junio hasta agosto del 2012. Los detalles de la anidación fueron registrados y se documentaron los tiempos de forrajeo sobre diversas especies florales, con las abejas preferentemente anidando en los tallos de madera de pasto de Rávena (Saccharum ravennae L.; Poales: Poaceae), los ciclos de vida duran de 28 a 32 dias, y las condiciones que ofrecen el potencial para un fácil manejo. Se destaca la importancia de este tipo de estudio sobre las abejas silvestres en Pakistán, igual que el desarrollo de sondeos bióticos sobre las abejas y la formación de melitólogos regionales, junto con actividades de extensión

New genera of meliturguline bees from Saudi Arabia and Persia, with notes on related genera and a key to the Arabian fauna (Hymenoptera: Andrenidae)

A new genus of melitturgine bees (Panurginae: Melitturgini) is described and figured from central Saudi Arabia. Belliturgula najdica Engel, gen. et sp. n., is similar in several respects to the genus Flavomeliturgula Patiny in that both have a greatly elongate glossa that is longer than the face and is truncate apically. The former differs in the greatly elongate and flattened first labial palpomere, the remaining palpomeres unmodified, the greatly protuberant clypeus, and long labrum lacking dense setal patches, among other traits. In addition, remarks are made on the composition of Flavomeliturgula, with Meliturgula deserta Warncke (Iran, Pakistan), removed to Khuzimelissa Engel, gen. n., resulting in the new combination Khuzimelissa deserta (Warncke), comb. n. Khuzimelissa differs from Flavomeliturgula by the unmodified labial palpomeres (lacking the elongate first three labial palpomeres of the latter genus), the acute glossa (broadly truncate in the latter), glossa shorter than head length (greater than head length in the latter), the abundant, white, squamiform setae of the mesoscutum (sparse, erect setae in the latter), cleft pretarsal claws (simple in the latter), presence of metasomal setal bands (lacking in the latter), and apically emarginate pygidial plate (acutely rounded in the latter). The species of Flavomeliturgula are organized into three subgenera, including Koreshomelissa Engel, subgen. n., and Freyamelissa Engel, subgen. n., and these may eventually warrant generic status once phylogenetic work on the tribe has been completed. A key to the Arabian genera of Panurginae is provided, along with an augmented key to the genera of subtribe Meliturgulina

New genera of meliturguline bees from Saudi Arabia and Persia, with notes on related genera and a key to the Arabian fauna (Hymenoptera: Andrenidae)

A new genus of melitturgine bees (Panurginae: Melitturgini) is described and figured from central Saudi Arabia. Belliturgula najdica Engel, gen. et sp. n., is similar in several respects to the genus Flavomeliturgula Patiny in that both have a greatly elongate glossa that is longer than the face and is truncate apically. The former differs in the greatly elongate and flattened first labial palpomere, the remaining palpomeres unmodified, the greatly protuberant clypeus, and long labrum lacking dense setal patches, among other traits. In addition, remarks are made on the composition of Flavomeliturgula, with Meliturgula deserta Warncke (Iran, Pakistan), removed to Khuzimelissa Engel, gen. n., resulting in the new combination Khuzimelissa deserta (Warncke), comb. n. Khuzimelissa differs from Flavomeliturgula by the unmodified labial palpomeres (lacking the elongate first three labial palpomeres of the latter genus), the acute glossa (broadly truncate in the latter), glossa shorter than head length (greater than head length in the latter), the abundant, white, squamiform setae of the mesoscutum (sparse, erect setae in the latter), cleft pretarsal claws (simple in the latter), presence of metasomal setal bands (lacking in the latter), and apically emarginate pygidial plate (acutely rounded in the latter). The species of Flavomeliturgula are organized into three subgenera, including Koreshomelissa Engel, subgen. n., and Freyamelissa Engel, subgen. n., and these may eventually warrant generic status once phylogenetic work on the tribe has been completed. A key to the Arabian genera of Panurginae is provided, along with an augmented key to the genera of subtribe Meliturgulina

A new species of the carpenter bee genus Xylocopa from the Sarawat Mountains in southwestern Saudi Arabia (Hymenoptera, Apidae)

A new species of the carpenter bee genus Xylocopa Latreille (Xylocopinae: Xylocopini) is described and figured from two localities in southern Saudi Arabia. Xylocopa (Koptortosoma) sarawatica Engel, sp. n. is a relatively small species similar to the widespread X. pubescens Spinola, but differs in the extent of maculation in males, setal coloration of both sexes, and male terminalia. A revised key to the species of Xylocopa in Saudi Arabia is provided

New genera of meliturguline bees from Saudi Arabia and Persia, with notes on related genera and a key to the Arabian fauna (Hymenoptera: Andrenidae)

A new genus of melitturgine bees (Panurginae: Melitturgini) is described and figured from central Saudi Arabia. Belliturgula najdica Engel, gen. et sp. n., is similar in several respects to the genus Flavomeliturgula Patiny in that both have a greatly elongate glossa that is longer than the face and is truncate apically. The former differs in the greatly elongate and flattened first labial palpomere, the remaining palpomeres unmodified, the greatly protuberant clypeus, and long labrum lacking dense setal patches, among other traits. In addition, remarks are made on the composition of Flavomeliturgula, with Meliturgula deserta Warncke (Iran, Pakistan), removed to Khuzimelissa Engel, gen. n., resulting in the new combination Khuzimelissa deserta (Warncke), comb. n. Khuzimelissa differs from Flavomeliturgula by the unmodified labial palpomeres (lacking the elongate first three labial palpomeres of the latter genus), the acute glossa (broadly truncate in the latter), glossa shorter than head length (greater than head length in the latter), the abundant, white, squamiform setae of the mesoscutum (sparse, erect setae in the latter), cleft pretarsal claws (simple in the latter), presence of metasomal setal bands (lacking in the latter), and apically emarginate pygidial plate (acutely rounded in the latter). The species of Flavomeliturgula are organized into three subgenera, including Koreshomelissa Engel, subgen. n., and Freyamelissa Engel, subgen. n., and these may eventually warrant generic status once phylogenetic work on the tribe has been completed. A key to the Arabian genera of Panurginae is provided, along with an augmented key to the genera of subtribe Meliturgulina

The ligational behavior of a phenolic quinolyl hydrazone towards copper(II)- ions

<p>Abstract</p> <p>Background</p> <p>The heterocyclic hydrazones constitute an important class of biologically active drug molecules. The hydrazones have also been used as herbicides, insecticides, nematocides, redenticides, and plant growth regulators as well as plasticizers and stabilizers for polymers. The importance of the phenolic quinolyl hydrazones arises from incorporating the quinoline ring with the phenolic compound; 2,4-dihydroxy benzaldehyde. Quinoline ring has therapeutic and biological activities whereas, phenols have antiseptic and disinfectants activities and are used in the preparation of dyes, bakelite and drugs. The present study is planned to check the effect of the counter anions on the type and geometry of the isolated copper(II)- complexes as well as the ligational behavior of the phenolic hydrazone; 4-[(2-(4,8-dimethylquinolin-2-yl)hydrazono)methyl] benzene-1,3-diol; (H₂L).</p> <p>Results</p> <p>A phenolic quinolyl hydrazone (H₂L) was allowed to react with various copper(II)- salts (Cl‾, Br‾, NO₃‾, ClO₄‾, AcO‾, SO₄^2-). The reactions afforded dimeric complexes (ClO₄‾, AcO‾ ), a binuclear complex (NO₃‾ ) and mononuclear complexes (the others; Cl‾, Br‾, SO₄^2-). The isolated copper(II)- complexes have octahedral, square pyramid and square planar geometries. Also, they reflect the strong coordinating ability of NO₃‾, Cl‾, Br‾, AcO‾ and SO₄^2-anions. Depending on the type of the anion, the ligand showed three different modes of bonding <it>viz</it>. (NN)⁰for the mononuclear complexes (<b>3, 4, 6</b>), (NO)^-with O- bridging for the dimeric complexes (<b>1, 5</b>) and a mixed mode [(NN)⁰+ (NO)^-with O- bridging] for the binuclear nitrato- complex (<b>2</b>).</p> <p>Conclusion</p> <p>The ligational behavior of the phenolic hydrazone (H₂L) is highly affected by the type of the anion. The isolated copper(II)- complexes reflect the strong coordinating power of the SO₄^2-, AcO‾, Br‾, Cl‾ and NO₃‾ anions. Also, they reflect the structural diversity (octahedral, square pyramid and square planar) depending on the type of the counter anion.</p

The ligational behavior of an isatinic quinolyl hydrazone towards copper(II)- ions

<p>Abstract</p> <p>Background</p> <p>The importance of the isatinic quinolyl hydrazones arises from incorporating the quinoline ring with the indole ring. Quinoline ring has therapeutic and biological activities whereas, the indole ring occurs in Jasmine flowers and Orange blossoms. As a ligand, the isatin moiety is potentially ambidentate and can coordinate the metal ions either through its lactam or lactim forms. In a previous study, the ligational behavior of a phenolic quinolyl hydrazone towards copper(II)- ions has been studied. As continuation of our interest, the present study is planned to check the ligational behavior of an isatinic quinolyl hydrazone.</p> <p>Results</p> <p>New homo- and heteroleptic copper(II)- complexes were obtained from the reaction of an isatinic quinolyl hydrazone (HL) with several copper(II)- salts <it>viz. </it>Clˉ, Brˉ, NO₃ˉ, ClO₄^-, SO₄^2-and AcO^-. The obtained complexes have O_h, T_dand D_4h- symmetry and fulfill the strong coordinating ability of Clˉ, Brˉ, NO₃ˉ and SO₄^2-anions. Depending on the type of the anion, the ligand coordinates the copper(II)- ions either through its lactam (NO₃ˉ and ClO₄^-) or lactim (the others) forms.</p> <p>Conclusion</p> <p>The effect of anion for the same metal ion is obvious from either the geometry of the isolated complexes (O_h, T_dand D_4h) or the various modes of bonding. Also, the obtained complexes fulfill the strong coordinating ability of Clˉ, Brˉ, NO₃ˉ and SO₄^2-anions in consistency with the donor ability of the anions. In case of copper(II)- acetate, a unique homoleptic complex (<b>5</b>) was obtained in which the AcO^-anion acts as a base enough to quantitatively deprotonate the hydrazone. The isatinic hydrazone uses its lactim form in most complexes.</p