Microbial Natural Products

The development of the microbiology industry has given rise to an urgent need to understand the concept of halal microbiology products. The halal status of microbiological products refers to the Fatwa of the Indonesian Ulema Council Number 1. The aim of this study is to explore the halalness of microbiological products through a comprehensive literature review, with a focus on the scope of microbiological products, halal status based on the MUI fatwa which provides halal fatwa on products that are certified halal in Indonesia. As a reference for giving fatwa, there is MUI Fatwa Number 1 of 2012 concerning the Use of Microbes and Microbiological Products. The halal status of microbiological products can be viewed from each stage of the manufacturing process, known as the Halal Critical Point (TKH). There are 6 TKH in the microbiological product production process which must be maintained so that they are not contaminated with haram and unclean materials, namely: starting with microbial culture (TKH 1), followed by the refreshing process (TKH 2), then the inoculum development stage (TKH 3) which is continued with product production in a bioreactor (TKH 4). After that, the product is harvested and continues with the product purification stage (TKH 5). In the final stage of production, stabilization is carried out and packaged until it becomes a final product that is ready to be marketed (TKH 6). By identifying halal critical points, the halal status of microbiological products can be traced so that they meet the criteria for halal products according to the MUI Fatwa.

Materials derived from plants (vegetable) are basically halal because there is no shari'a argument which specifically mentions the prohibition of the types of materials derived from plants, but if they have been processed using additives or processing aids that are not halal then the status of the product may become non-halal.. This paper uses a review of literature from various main references in the criteria for halal certification and knowledge of materials and processing of plant-based products. Identification of critical points for vegetable ingredients can be analyzed using a decision tree for identifying critical points for halal vegetable ingredients. Products derived from vegetable materials can be contaminated with unclean/unclean materials if there are additional ingredients and processing. The various processed plant food products in this article are complemented by the results of a study identifying their critical points starting from dried plant materials, wheat flour to starch and its derivatives. Vegetable ingredients are doubtful and their halal status needs to be criticized if they have undergone processing and the use of additional ingredients.

Livestock production is a fundamental pillar of the Moroccan economy. Infectious diseases of cattle and other species represent a significant threat to the livestock industry, animal health, and food safety and security. Bovine tuberculosis (bTB), mainly caused by Mycobacterium bovis (M. bovis), generates considerable direct and indirect economic losses, in addition to the unknown human health burden caused by zoonotic transmission. Previous studies have suggested likely M. bovis transmission links between Morocco and Southern Europe, however, limitations inherent with the methods used prevented more definitive conclusions from being drawn. In this study, we employed whole genome sequencing analysis of a large set of M. bovis isolates to better define the phylogenetic links between strains from Morocco and neighboring countries. A total of 780 M. bovis sequences representing 36 countries were included in the study. The results of SNP analysis showed a close genetic relationship between M. bovis from Morocco and each of Spain, France, Portugal and Germany, this is supported by animal trade between Morocco and these countries, in addition to the important human migration from Morocco to Europe and North America. Regarding zoonotic tuberculosis (TB) transmission, we were able to find genetic links between M. bovis isolates from cattle in Morocco and humans in Italy, Germany, and the UK. These results support our hypothesis of significant transmission of M. bovis from cattle to humans, which calls for further investigations of zoonotic TB transmission in Morocco and in other countries. 105 and is also made available for use under a CC0 license.

Primeiramente a Deus, que me deu muita saúde, paz, serenidade e forças para seguir nesse caminho árduo até o final, conciliando entre a vida acadêmica e profissional (mestrado/emprego). À minha amada Luana, que é minha noiva, companheira, amiga, cúmplice, enfim, tudo na minha vida e sempre acreditou em mim e está sempre ao meu lado me incentivando e dando forças. Eu te amo, minha Luana! Aos meus sogros, Maria de Lourdes e José Cláudio, que fazem tudo por mim, me tratam como um filho e sempre acreditaram na minha vitória. Aos meus pais, Edualdo e Ana Maria (in memoriam), que me criaram e proporcionaram o melhor possível em minha vida. Foi por causa de vocês que me tornei o que sou hoje e cheguei até aqui. Muito obrigado por tudo! Aos orientadores Dr. Fabrício e Dr. Floriano, que não tenho palavras para agradecer a paciência e a dedicação que tiveram comigo. Sempre confiaram no meu trabalho, me mostraram que eu posso ser melhor, ser mais crítico, mais atento, aprender mais, ler mais e sempre evoluir não apenas na vida acadêmica, na minha vida como um todo e me guiaram com extrema competência até aqui. Os recomendo a quaisquer candidatos ao programa. Gratidão eterna! Aos amigos Cristiano Braga, Felipe Gil e Leandro Leal, que além de colegas de profissão se tornaram meus amigos e "seguraram a barra" das minhas saídas e faltas no trabalho para cursar as disciplinas no meio do expediente e me ajudavam a me manter calmo, acreditar mais e aguentar esse ritmo tão intenso. À Fundação Oswaldo Cruz, que confiou em mim e me deu a oportunidade de realizar meu sonho de me tornar mestre, fazer parte do programa e poder aplicar meus conhecimentos em prol da sociedade, apresentando um trabalho de qualidade e um resultado que pode colaborar com a comunidade científica de alguma maneira. Minha estadia aqui mudou minha vida e vou levar comigo pra sempre, muito obrigado! Ao Dr. Nicolas Carels por ter aceitado ser revisor deste trabalho e ser tão solícito e ter dado muitas sugestões para a melhoria deste documento. A Lídia Maria Castanheira, minha tia e madrinha, que dedicou um pouco do seu tempo para ler este trabalho e dar uma ajuda na melhoria de escrita, analisando o português, além de sempre acreditar em mim e ser uma pessoa muito boa para mim. A todos os envolvidos na coordenação da BCS, que estiveram comigo em todos os momentos do curso (por exemplo, no momento que precisei fazer uma cirurgia e foi necessário adiar minha qualificação naquela ocasião). A todos os integrantes do grupo de pesquisa de bactérias multirresistentes e aos nobres colegas do PROCC. A todos aqueles que participaram direta ou indiretamente e que, de alguma forma, contribuíram para minha formação, o meu mais sincero agradecimento. v "No fim dá tudo certo e se ainda não deu certo é porque não chegou ao fim.

Healthcare-associated infections (HAI) is a serious public health problem. They may be associated with morbidity and mortality and are responsible for increases in patient hospitalization. In this context, it is important to identify strategies that may prevent the spread of bacteria in hospitalized patients. In this work, we propose a new method to identify therapeutic targets through the analysis of metabolic networks on genomic scale, which enables the identifies known and potential targets in multidrug resistant bacteria. Here we automate the process of identifying essential genes using Flux Balance Analysis (FBA), Flux Variability Analysis (FVA), and queries to various public repositories such as KEGG, Uniprot and Drugbank The web application was developed in Python using CobraPy and Django 1.11. Genomic scale metabolic networks, available in the SBML format, were analyzed using this tool. Information on therapeutic targets and possible drugs was found as a result of the analys...

Mycobacterial species in nature are found in abundance in sphagnum peat bogs where they compete for nutrients with a variety of microorganisms including fungi. We screened a collection of fungi isolated from sphagnum bogs by co-culture with Mycobacterium tuberculosis (Mtb) to look for inducible expression of antitubercular agents and identified 5 fungi that produced cidal antitubercular agents upon exposure to live Mtb. Whole genome sequencing of these fungi followed by fungal RNAseq after Mtb exposure allowed us to identify biosynthetic gene clusters induced by co-culture. Three of these fungi induced expression of patulin, one induced citrinin expression and one induced the production of nidulalin A. The biosynthetic gene clusters for patulin and citrinin have been previously described but the genes involved in nidulalin A production have not been described before. All 3 of these potent electrophiles react with thiols and treatment of Mtb cells with these agents followed by Mtb RNAseq showed that these natural products all induce profound thiol stress suggesting a rapid depletion of mycothiol. The induction of thiol-reactive mycotoxins through 3 different systems in response to exposure to Mtb suggests that fungi have identified this as a highly vulnerable target in a similar microenvironment to that of the caseous human lesion.

Antibioticos ou antimicrobianos, sao drogas naturais ou sinteticas capazes de inibir o crescimento microbiano(bacteriostaticos) ou causar a morte das bacterias (bactericidas). Os antimicrobianos correspondem a uma classede farmacos que e consumida frequentemente em hospitais e ambulatorios. Entretanto, sao os unicos agentesfarmacologicos que nao afetam somente aos pacientes que os utilizam, mas tambem interferem de forma significativano ambiente hospitalar por alteracao da ecologia microbiana. O uso indiscriminado e nao racional destesfarmacos provoca, a medio e longo prazo, a resistencia bacteriana aumentando a duracao das doencas e possivelobito. Os custos dos cuidados de saude tambem aumentam com internacoes mais prolongadas e a necessidadede cuidados intensivos. O presente estudo e uma revisao de literatura, tendo como objetivo especifico discorrersobre o mecanismo de acao das diferentes classes de antibioticos e o mecanismo de resistencia desenvolvido pelasbacterias. A busca po...

Citation for published version (APA): Abdel-Mageed, W. M., Lehri, B., Jarmusch, S. A., Miranda, K., Al-Wahaibi, L. H., Stewart, H. A., Jamieson, A. J., Jaspars, M., & Karlyshev, A. V. (2020). Whole genome sequencing of four bacterial strains from South Shetland Trench revealing biosynthetic and environmental adaptation gene clusters. Marine Genomics, 54, [100782]. https://doi.org/10.1016/j.margen.2020.100782

Mycobacterial species in nature are found in abundance in sphagnum peat bogs where they compete for nutrients with a variety of microorganisms including fungi. We screened a collection of fungi isolated from sphagnum bogs by co-culture with Mycobacterium tuberculosis (Mtb) to look for inducible expression of antitubercular agents and identified five fungi that produced cidal antitubercular agents upon exposure to live Mtb. Whole genome sequencing of these fungi followed by fungal RNAseq after Mtb exposure allowed us to identify biosynthetic gene clusters induced by co-culture. Three of these fungi induced expression of patulin, one induced citrinin expression and one induced the production of nidulalin A. The biosynthetic gene clusters for patulin and citrinin have been previously described but the genes involved in nidulalin A production have not been described before. All three of these potent electrophiles react with thiols and treatment of Mtb cells with these agents followed by Mtb RNAseq showed that these natural products all induce profound thiol stress suggesting a rapid depletion of mycothiol. The induction of thiol-reactive mycotoxins through three different systems in response to exposure to Mtb suggests that fungi have identified this as a highly vulnerable target in a similar microenvironment to that of the caseous human lesion.

Staphylococcus species have capability to produce pigments such as carotenoids, melanin and staphloxanthin which can be used in the applications of industries such as food, pharmaceuticals and cosmetics. Hence, the objective of this paper was to isolate, optimize, characterize and identify of pigment-producing bacterial from soil, water, food around Ogwa, Esan West Local Government Area of Edo State, Nigeria using appropriate standard techniques. The microbial load of the bacterial isolates ranges from 2.20x10 4 cfu/ml to 7.0x10 4 cfu/ml. All the isolates produced a yellow-colored pigment. During optimization studies, maximum pigment production was observed at pH range of 5 to 7, the temperature of 30, 37 and 42 ℃, inoculum size up to 1% with NaCl concentration of 0.5%, OD at 540 nm respectively. It was observed that peptone worked best for enhancement of pigment production. This findings showed that the bacterial isolates were able to produce pigments under the influence of different nutrition and environmental variability implementing that the bacteria are potential sources for the synthesis of pigments in industries. Hence, the objective of this paper is to isolation, optimization, characterization and identification of pigment-producing bacterial from soil, water, food around Ogwa,

Resumo: O aumento da resistência a múltiplas drogas em algumas linhagens de microorganismos tem sido registrado em todo o mundo. Conseqüentemente, os corriqueiros antibióticos orais estão perdendo sua eficácia no tratamento de infecções causadas por ...

The excessive use of pesticides causesmaximum soil stress and infertile conditions. The present study was performed in order to explore and identify the novel microbial source for the biodegradation of monocrotophos pesticides. Soil samples (approx. 500 g) were collected using some clean,dry, and sterile polythene bags along with a sterile spatula, marking pen rubber band, and other accessories. These samples were air-dried for 1 week, crushed, and sieved. The sieved soils were then used for Actinomycetes isolation. A totalof 120 Soil samples were aseptically collected from different field regions of Uttarakhand viz. Tehri-Garhwal, Chamoli, Srinagar, Uttarkashi, and Haridwar havedominant usage of monocrotophos pesticides. Amongst these samples, A total of 280 microbes were isolated; out of which 24 isolates of Actinobacteria (8.57 %) were isolated. The results revealed the strains of the genera viz. Micromonospora (65%), Actinomycetes (25%,) and Streptomyces (10%)are meant to be res...

Aclacinomycin methylesterase (RdmC) is one of the tailoring enzymes that modify the aklavinone skeleton in the biosynthesis of anthracyclines in Streptomyces species. The crystal structures of this enzyme from Streptomyces purpurascens in complex with the product analogues 10-decarboxymethylaclacinomycin T and 10decarboxymethylaclacinomycin A were determined to nominal resolutions of 1.45 and 1.95 Å, respectively. RdmC is built up of two domains. The larger ␣/␤ domain shows the common ␣/␤ hydrolase fold, whereas the smaller domain is ␣-helical. The active site and substrate binding pocket are located at the interface between the two domains. Decarboxymethylaclacinomycin T and decarboxymethylaclacinomycin A bind close to the catalytic triad (Ser 102-His 276-Asp 248) in a hydrophobic pocket, with the sugar moieties located at the surface of the enzyme. The binding of the ligands is dominated by hydrophobic interactions, and specificity appears to be controlled mainly by the shape of the binding pocket rather than through specific hydrogen bonds. Mechanistic key features consistent with the structure of complexes of RdmC with product analogues are Ser 102 acting as nucleophile and transition state stabilization by an oxyanion hole formed by the backbone amides of residues Gly 32 and Met 103 .

12-deoxy-nogalonic acid oxygenase (SnoaB) catalyzes the oxygenation of 12deoxy-nogalonic acid at position 12 to yield nogalonic acid, which is one of the steps in the biosynthesis of the polyketide nogalamycin in Streptomyces nogalater. SnoaB belongs to a family of small cofactor-free oxygenases which carry out oxygenation reactions without the aid of any prosthetic group, cofactor or metal ion. Recombinant SnoaB was crystallized in space group P2 1 2 1 2, with unit-cell parameters a = 58.8, b = 114.1, c = 49.5 Å , and these crystals diffracted to 2.4 Å resolution. Recombinant SnoaB does not contain any methionine residues and three double mutants were designed and produced for the preparation of selenomethionine-substituted samples. The selenomethioninesubstituted mutant F40M/L89M crystallized in the same space group as the native enzyme.

The excessive use of pesticides causesmaximum soil stress and infertile conditions. The present study was performed in order to explore and identify the novel microbial source for the biodegradation of monocrotophos pesticides. Soil samples (approx. 500 g) were collected using some clean,dry, and sterile polythene bags along with a sterile spatula, marking pen rubber band, and other accessories. These samples were air-dried for 1 week, crushed, and sieved. The sieved soils were then used for Actinomycetes isolation. A totalof 120 Soil samples were aseptically collected from different field regions of Uttarakhand viz. Tehri-Garhwal, Chamoli, Srinagar, Uttarkashi, and Haridwar havedominant usage of monocrotophos pesticides. Amongst these samples, A total of 280 microbes were isolated; out of which 24 isolates of Actinobacteria (8.57 %) were isolated. The results revealed the strains of the genera viz. Micromonospora (65%), Actinomycetes (25%,) and Streptomyces (10%)are meant to be res...

Dipyridamole is an antithrombotic agent that is widely used in the treatment of many vascular disorders. Also, the prostacyclin analogue iloprost has been utilized to salvage limbs in patients with severe limb ischemia. In this study we investigated whether dipyridamole and iloprost have anti-angiogenic properties and their anti-angiogenic properties were compared to bevacizumab, a known inhibitor of angiogenesis, using the in vivo chick chorioallantoic membrane animal model. Agar pellets were prepared with three different drug concentrations at 10-6 M, 10-5 M, and 10-4 M. For each drug concentration twenty fertilized eggs were used. The entire experiment was performed in duplicate. Blood vessel density and loss were examined and scored under a stereoscopic microscope. For the 10-4 M, 10-5 M and 10-6 M concentrations, the anti-angiogenic scores of iloprost were 0.2, 0.1 and 0.05, respectively. In the same order, the anti-angiogenic scores for dipyridamole were 0.2, 0.3 and 0.8. The ...

Drug resistant and opportunistic organisms are a problem to medical health due to the fact that most of the drugs that were used are now not effective. Currently, there is a need to search for new drugs that can enhance the control of these organisms. Actinomycetes and their secondary metabolites can be used as such drugs. This study was designed to isolate actinomycetes producing novel anti-fungal compounds from waste dump soil in Western Uganda. Fifty six (56) actinomycetes were isolated from 22 waste dump soil samples. All isolates were screened using modified spektra-plak method against Candida albicans ATCC1023, Penicillium sp., Aspergillus sp., Fusarium sp. and Rhizopus sp. Eight 8(14.29%) isolates showed antifungal activity to at least one test fungi during primary screening. Two isolates [KBRWDSa (FR) and KBMWDSb6] showed activity to all test fungi. Secondary screening was carried out by growing all 56 isolates in broth and their supernatant was tested for antifungal activity using agar well diffusion method. 11(19.64%) of these isolates showed activity against at least one test fungi with mean zone of inhibition 5.33 to 29.69 mm. Isolate KBMWDSb6 showed a broad spectrum activity against all test fungi. The remaining broths were extracted using ethanol. The ethanol extract at 2.5 mg/ml concentration was also tested for antifungal activity using agar well diffusion method. 13 (23.21%) isolates showed activity against at least one test fungi with mean zone of inhibition 6.33 to 30.67mm. The findings showed that some of these isolates had antifungal activity.

Whole genome sequences of four bacterial strains Dietzia maris SST1, Pseudomonas zhaodongensis SST2, Pseudomonas sp. SST3 and Halomonas sulfidaeris SST4, recovered from the South Shetland Trench sediment in Antarctica were analyzed using Ion Torrent sequencing technology. The respective sizes of their genomes (3.88, 4.99, 5.60 and 4.25 Mb) and GC contents (70.0, 60.3, 59.9 and 53.8%) are in agreement with these values of other strains of the species. The bacterial strains displayed promising antimicrobial activity against a number of pathogenic bacterial and fungal species. Whole genomes have been assembled and biosynthetic gene clusters (BGCs) have been identified using the antibiotics and Secondary Metabolite Analysis Shell (antiSMASH) web platform. Comparative analysis of the genome sequences revealed that the strains host abundant BGCs encoding for terpenes, siderophores, arylpolyene, bacteriocins, and lassopeptides. Furthermore, the key stress-related genes were identified and their distribution provided an insight into how these isolates adapt to key marine environmental conditions. This comprehensive study is a contribution to understanding the nature of life on the deepsea environments.

The main protease (Mpro) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to the Lipinski’s rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good binding affinities towards the molecular dynamic simulation (MDS)-derived enzyme’s conformers. Final MDS experiments were performed on the ligand–protein complexes (compounds 1–12, Table S1) to verify their binding modes and calculate their binding free energy. Consequently, a final selection of six compounds (1–6) was proposed to possess high potential as anti-SARS-CoV-2 drug candidates. Our study provides insight into the role of the Mpro structural flexibility during interactions with the possible inhib...

Here we present the physiological features of Pseudomonas extremaustralis strain USBA-GBX-515 (CMPUJU 515), isolated from soils in Superparamo ecosystems, > 4000 m.a.s.l, in the northern Andes of South America, as well as the thorough analysis of the draft genome. Strain USBA-GBX-515 is a Gram-negative rod shaped bacterium of 1.0-3.0 μm × 0.5-1 μm, motile and unable to form spores, it grows aerobically and cells show one single flagellum. Several genetic indices, the phylogenetic analysis of the 16S rRNA gene sequence and the phenotypic characterization confirmed that USBA-GBX-515 is a member of Pseudomonas genus and, the similarity of the 16S rDNA sequence was 100% with P. extremaustralis strain CT14-3T. The draft genome of P. extremaustralis strain USBA-GBX-515 consisted of 6,143,638 Mb with a G + C content of 60.9 mol%. A total of 5665 genes were predicted and of those, 5544 were protein coding genes and 121 were RNA genes. The distribution of genes into COG functional categor...

Antibióticos são compostos farmácos naturais ou sintéticos capazes de inibir o crescimento ou causar a morte das bactérias, está, por sua vez, possui grande capacidade de adaptação estando associada à estrutura genômica, que garante a troca de genes entre as bactérias, utilizando elementos não cromossômicos: plasmídios, transposons e até bacteriófagos. Os fármacos existentes atualmente, com esta finalidade, interrompem a replicação e o reparo do DNA bacteriano. Todavia as bactérias podem tornar-se resistentes aos fármacos por alguns mecanismos, como as mutações cromossômicas e genéticas, desenvolvimento da capacidade de produzir bombas de resistências a múltiplos fármacos (MDR) e destruição do antibiótico através de enzimas. Dessa forma, objetivou-se descrever os mecanismos da farmacodinâmica dos antibióticos, ressaltando seu mecanismo de resistência e principais eventos adversos, por meio de uma revisão bibliográfica, utilizando livros disponíveis, Google acadêmico, PubMed e Scielo, e dessa forma abrir portas para estudos mais complexos. Após a realização deste trabalho, foi possível perceber que o combate à resistência bacteriana é um problema de saúde pública mundial e deve ser abordado sob vários aspectos, entre as causas para este fenômeno está o uso abusivo e indiscriminado de antibióticos.

A Micromonospora strain, isolate MT25T, was recovered from a sediment collected from the Challenger Deep of the Mariana Trench using a selective isolation procedure. The isolate produced two major metabolites, n-acetylglutaminyl glutamine amide and desferrioxamine B, the chemical structures of which were determined using 1D and 2D-NMR, including 1H-15N HSQC and 1H-15N HMBC 2D-NMR, as well as high resolution MS. A whole genome sequence of the strain showed the presence of ten natural product-biosynthetic gene clusters, including one responsible for the biosynthesis of desferrioxamine B. Whilst 16S rRNA gene sequence analyses showed that the isolate was most closely related to the type strain of Micromonospora chalcea, a whole genome sequence analysis revealed it to be most closely related to Micromonospora tulbaghiae 45142T. The two strains were distinguished using a combination of genomic and phenotypic features. Based on these data, it is proposed that strain MT25T (NCIMB 15245T, T...

The textile industry is one amongst the rapidly growing industries world wide, which utilizes enormous amounts of synthetic dyes. Consequently, the effluent from these textile industries poses serious threat to the environment which is often very difficult to treat and dispose. This has become a very grave problem in environment conservation and hence natural pigments have drawn the attention of industry as safe alternative. In this context, in the present study an attempt was made to bioprospect marine bacteria towards isolation of a suitable and ideal pigment that could be used as a natural dye. A marine Serratia sp. BTWJ8 was recognized to synthesize enormous amounts of a prodigiosin-like pigment. The pigment was isolated and characterized for various properties. The pigment was evaluated for application as a dye in the textile industry. Results of the studies indicated that this pigment could be used as a natural dye for imparting red-yellow colour to various grades of textile materials. The colour was observed to be stable after wash performance studies.

Antibiotic resistance has been growing at an alarming rate and consequently the arsenal of effective antibiotics against Gram-negative and Gram-positive bacteria has dropped dramatically. In this sense there is a strong need to produce new substances that not only have good spectrum of activity, but having new mechanisms of action. In this regard, this paper emphasizes the coordination of metals to antibiotics as a strategy for reversing antibiotic resistance and production of new drugs, with a special focus on quinolones, fluoroquinolones, sulfonamides and tetracyclines.

Four compounds (1–4) were isolated from the extracts of Streptomyces sp. CT37 using bioassay in conjunction with mass spectrometric molecular networking (MN) driven isolation. Their complete structures were established by high-resolution electrospray ionization mass spectrometry (HR-ESIMS), and 1D and 2D nuclear magnetic resonance (NMR) data. Legonimide 1 was identified as a new alkaloid containing a rare linear imide motif in its structure, while compounds 2–4 were already known and their structures were elucidated as 1H-indole-3-carbaldehyde, actinopolymorphol B, (2R,3R)-1-phenylbutane-2,3-diol, respectively. The biosynthetic pathways of 1–4 were proposed based on the reported biogenesis of indole alkaloids in literature. Bioactivity tests for 1 and 2 revealed moderate growth inhibition activity against Candida albicans ATCC 10231 with MIC95 values of 21.54 µg/mL and 11.47 µg/mL, respectively.

Citation for published version (APA): Abdel-Mageed, W. M., Lehri, B., Jarmusch, S. A., Miranda, K., Al-Wahaibi, L. H., Stewart, H. A., Jamieson, A. J., Jaspars, M., & Karlyshev, A. V. (2020). Whole genome sequencing of four bacterial strains from South Shetland Trench revealing biosynthetic and environmental adaptation gene clusters. Marine Genomics, 54, [100782]. https://doi.org/10.1016/j.margen.2020.100782

Recebido em 26/2/09; aceito em 21/8/09; publicado na web em 24/2/10 ANTIBIOTICS: THERAPEUTIC IMPORTANCE AND PERSPECTIVES FOR THE DISCOVERY AND DEVELOPMENT OF NEW AGENTS. There is a continuous need for antibiotics, mainly with new mechanisms of action, since infectious diseases represent the second major cause of death in the world and bacteria resistance levels are high. This review describes the contribution of microbial natural products for the development of the major antibiotic classes, the mechanisms of action of current antibiotics, some modern approaches involving genetic tools for the discovery and development of new antibiotics from microbial products and antibiotics in clinical trials.

Recebido em 15/1/09; aceito em 11/3/09; publicado na web em 2/4/09 MARINE ORGANISMS AS A SOURCE OF NEW PHARMACEUTICALS: HISTORY AND PERSPECTIVES. Though sharing only a short part on the natural products timeline, the studies on marine products has already handed in four new drugs to the clinical arsenal and brought up a long and promising list of unique molecules to pre-clinical and clinical trials. Thus, as the available analytical resources improve and the interest of large pharmaceutical companies arises, medical use of marine products has definitely become a reality.

Dipyridamole is an antithrombotic agent that is widely used in the treatment of many vascular disorders. Also, the prostacyclin analogue iloprost has been utilized to salvage limbs in patients with severe limb ischemia. In this study we investigated whether dipyridamole and iloprost have anti-angiogenic properties and their anti-angiogenic properties were compared to bevacizumab, a known inhibitor of angiogenesis, using the in vivo chick chorioallantoic membrane animal model. Agar pellets were prepared with three different drug concentrations at 10-6 M, 10-5 M, and 10-4 M. For each drug concentration twenty fertilized eggs were used. The entire experiment was performed in duplicate. Blood vessel density and loss were examined and scored under a stereoscopic microscope. For the 10-4 M, 10-5 M and 10-6 M concentrations, the anti-angiogenic scores of iloprost were 0.2, 0.1 and 0.05, respectively. In the same order, the anti-angiogenic scores for dipyridamole were 0.2, 0.3 and 0.8. The ...

Prodigiosin (Pg) is a bright red pigment, which is produced by gram negative and gram positive bacteria including Serratia marcescens, Hahella chejuensis, Vibrio psychroerythrus, Streptomyces coelicolor and many other marine bacteria such as Pseudomonas sp., Vibrio sp. Pg induces apoptosis in different kinds of cancer cells with low toxicity on normal cells. In this study, we purified Pg from solid fermentation of S. marcescens M10 strain and assessed its anticancer activity in tumorized mice. The results showed that Pg was purified by running through a silicagel 60 column with a suitable solvent system of n-hexane:toluene at the rate of 1:1 (v/v) combined with toluene:ethyl acetate at the rate of 9:1 (v/v). TLC plate was used to test the presence of active substances with separation solvent n-hexane:ethyl acetate ratio of 1:1 (v/v). The purity of fractions tested by high performance liquid chromatography method showed as 98%. Purified fractions also showed promising anti-tumor acti...

Recebido em 10/12/04; aceito em 29/6/05; publicado na web em 20/1/06 THE NATURAL PRODUCTS AND THE MODERN MEDICINAL CHEMISTRY. Natural products have been utilized by humans since ancient times and the relief and cure of their diseases was the first purpose for using natural products in medicine. The history of the oriental and occidental civilizations is very rich in examples of the utilization of natural products in medicine and health care. Chinese traditional medicine is one of the most important examples of how natural products can be efficient in the treatment of diseases, and it points to the importance of scientific research on natural products, concerning the discovery of new active chemical entities. The complexity, chemical diversity and biological properties of natural products always fascinated people, and during the last 200 years, this led to the discovery of important new drugs. In the last 30 years, the development of new bioassay techniques, biotechnology methods, bio-guided phytochemical studies, automated high throughput screening and high performance analytical methods, have introduced new concepts and possibilities of rational drug design and drug discovery. In this context, natural products have played an important and decisive role in the development of modern medicinal chemistry.

Recebido em 10/12/04; aceito em 29/6/05; publicado na web em 20/1/06 THE NATURAL PRODUCTS AND THE MODERN MEDICINAL CHEMISTRY. Natural products have been utilized by humans since ancient times and the relief and cure of their diseases was the first purpose for using natural products in medicine. The history of the oriental and occidental civilizations is very rich in examples of the utilization of natural products in medicine and health care. Chinese traditional medicine is one of the most important examples of how natural products can be efficient in the treatment of diseases, and it points to the importance of scientific research on natural products, concerning the discovery of new active chemical entities. The complexity, chemical diversity and biological properties of natural products always fascinated people, and during the last 200 years, this led to the discovery of important new drugs. In the last 30 years, the development of new bioassay techniques, biotechnology methods, bio-guided phytochemical studies, automated high throughput screening and high performance analytical methods, have introduced new concepts and possibilities of rational drug design and drug discovery. In this context, natural products have played an important and decisive role in the development of modern medicinal chemistry.

In economic terms, biodiversity transcends the boundaries usually given to conventional industries because it is a valuable source of biological and chemical data of great use to drug discovery. Certainly, the use of natural products has been the single most successful strategy in the discovery of novel medicines, and most of the medical breakthroughs are based on natural products. Half of the top 20 best-selling drugs are natural products, and their total sales amounted to US$ 16 billions shows the importance of natural products, which is evidenced by the new chemical entities (NCE) approved by regulatory authorities around the world in the past decade. Recently, the approval of the alkaloid galanthamine as a medicine to treat Alzheimer's disease shows that natural compounds from plants will continue to reach the market. The huge biological diversity of the Brazilian biomes, by its ability to generate new knowledge and technological innovation can be a fantastic alternative as raw material for drug discovery.

The textile industry is one amongst the rapidly growing industries world wide, which utilizes enormous amounts of synthetic dyes. Consequently, the effluent from these textile industries poses serious threat to the environment which is often very difficult to treat and dispose. This has become a very grave problem in environment conservation and hence natural pigments have drawn the attention of industry as safe alternative. In this context, in the present study an attempt was made to bioprospect marine bacteria towards isolation of a suitable and ideal pigment that could be used as a natural dye. A marine Serratia sp. BTWJ8 was recognized to synthesize enormous amounts of a prodigiosin-like pigment. The pigment was isolated and characterized for various properties. The pigment was evaluated for application as a dye in the textile industry. Results of the studies indicated that this pigment could be used as a natural dye for imparting red-yellow colour to various grades of textile materials. The colour was observed to be stable after wash performance studies.

Context: Although there is an abundance of several microbial phyla in the oceans actinobacteria have emerged as a major source for natural products. Streptomyces sps is the widely encountered actinobacteria. Lately, Streptomyces are increasingly been used for pigment extraction. Aim: The aim herein was to extract bioactive melanin pigment from rare actinobacteria, which is a not a widespread occurrence. Materials and Methods: Marine samples were collected aseptically from the waters of the Arabian Sea, Allepey, Kerala, India. Isolation was performed by serial dilution method upon dry heat treatment and pre-enrichment technique on Actinomycetes Isolation Agar. Selected potent isolates were fermented and the pigments were extracted. Thereafter the pigment was analyzed by various techniques viz., thin layer chromatography, UV-Visible spectrophotometry and Fourier Transfer Infra Red spectroscopy. Further, the pigment was evaluated for its antibacterial, anti-biofilm and anti-quorum sensing potential. Results: The isolates were designated as JN1 and JN2 and their respective extracts JN1M and JN2M. JN1M was found to be inhibiting biofilm forming clinical isolate Staphylococcus sp. showing an activity of 64.20 ± 3.33% and pigment from JN2M 65.99± 2.81%. The melanin pigment also exhibited considerable activity against various human pathogens. The isolate JN1 was identified as Nocardiopsis dassonvillei strain JN1 (accession number: KX263302) and JN2 as Nocardiopsis sp (accession number: KX263303) by conventional and molecular techniques. Conclusion: With reference to previous reports, this is one of the very few reports of marine Nocardiopsis dassonvillei exhibiting melanin production. Thus it has established the production of melanin from rare actinomycetes, N. dassonvillei in specific.

Although the production of the secondary metabolite is frequently restricted, methods to regulate and optimize their synthesis are extremely beneficial. The current study proposes to enhance the production of antibiofilm metabolite in Streptomyces cellulosae (S. cellulosae). It was isolated from soil by growing on Gause's media and identified by colony morphology and genomic sequencing of 16S rDNA. Antibacterial and antibiofilm activities of the isolates were screened against a series of pathogenic bacteria by agar plug diffusion and 96 well microtiter plate methods, respectively. Physiological regulation of the bacterial bioactivity against biofilm formation was monitored under different cultural conditions. The isolated Streptomyces sequence analysis of the 16S rDNA was 100% identical to the sequence of S. cellulosae strain NBRC 13027. Physical (temperature and pH) and chemical (carbon, nitrogen, and minerals) culture medium factors have shown variable impacts on the growth and bioactive substances of S. cellulosae. Moreover, results of simple linear regression and correlation suggested that most of the physiological regulations with the highest response (r2= 0.85-0.99; p<0.01) and linearly (r= 0.88-0.99; p<0.01) were correlated between microbial biomass and crude extract. Lastly, under different culture growth conditions, biofilm inhibition was tested against Pseudomonas aeruginosa (P. aeruginosa). The physiological regulation results exhibited that 1 μg/mL of the extract was the most efficient concentration against biofilm formation in P. aeruginosa while 3 μg/mL is an effective bactericidal dose against P. aeruginosa. We concluded that S. cellulosae can produce antibacterial and antibiofilm metabolites. Physiological regulation is considered a powerful tool that can be used for increasing the biosynthesis of the active metabolites and biomass.

Here we present the physiological features of Pseudomonas extremaustralis strain USBA-GBX-515 (CMPUJU 515), isolated from soils in Superparamo ecosystems, &gt; 4000 m.a.s.l, in the northern Andes of South America, as well as the thorough analysis of the draft genome. Strain USBA-GBX-515 is a Gram-negative rod shaped bacterium of 1.0-3.0 μm × 0.5-1 μm, motile and unable to form spores, it grows aerobically and cells show one single flagellum. Several genetic indices, the phylogenetic analysis of the 16S rRNA gene sequence and the phenotypic characterization confirmed that USBA-GBX-515 is a member of Pseudomonas genus and, the similarity of the 16S rDNA sequence was 100% with P. extremaustralis strain CT14-3T. The draft genome of P. extremaustralis strain USBA-GBX-515 consisted of 6,143,638 Mb with a G + C content of 60.9 mol%. A total of 5665 genes were predicted and of those, 5544 were protein coding genes and 121 were RNA genes. The distribution of genes into COG functional categor...

Resumo: Enterococcus sp fazem parte da flora bacteriana gastrointestinal normal do Homem e dos animais, podendo ocasionalmente provocar infecções, sobretudo em a indivíduos com imunossupressão ou outros factores de predisposição como a utilização ...

Antibiotic resistance has been growing at an alarming rate and consequently the arsenal of effective antibiotics against Gram-negative and Gram-positive bacteria has dropped dramatically. In this sense there is a strong need to produce new substances that not only have good spectrum of activity, but having new mechanisms of action. In this regard, this paper emphasizes the coordination of metals to antibiotics as a strategy for reversing antibiotic resistance and production of new drugs, with a special focus on quinolones, fluoroquinolones, sulfonamides and tetracyclines.

The genus Photobacterium is known for its ecophysiological versatility encompassing free-living, symbiotic, and pathogenic lifestyles. Photobacterium sp. CCB-ST2H9 was isolated from estuarine sediment collected at Matang Mangrove, Malaysia. In this study, the genome of CCB-ST2H9 was sequenced, and the pan-genome of 37 Photobacterium strains was analysed. Phylogeny based on core genes showed that CCB-ST2H9 clustered with P. galatheae, forming a distinct clade with P. halotolerans, P. salinisoli, and P. arenosum. The core genome of Photobacterium was conserved in housekeeping functions, while the flexible genome was well represented by environmental genes related to energy production and carbohydrate metabolism. Genomic metrics including 16S rRNA sequence similarity, average nucleotide identity, and digital DNA–DNA hybridization values were below the cut-off for species delineation, implying that CCB-ST2H9 potentially represents a new species. Genome mining revealed that biosynthetic ...

Antibióticos são compostos farmácos naturais ou sintéticos capazes de inibir o crescimento ou causar a morte das bactérias, está, por sua vez, possui grande capacidade de adaptação estando associada à estrutura genômica, que garante a troca de genes entre as bactérias, utilizando elementos não cromossômicos: plasmídios, transposons e até bacteriófagos. Os fármacos existentes atualmente, com esta finalidade, interrompem a replicação e o reparo do DNA bacteriano. Todavia as bactérias podem tornar-se resistentes aos fármacos por alguns mecanismos, como as mutações cromossômicas e genéticas, desenvolvimento da capacidade de produzir bombas de resistências a múltiplos fármacos (MDR) e destruição do antibiótico através de enzimas. Dessa forma, objetivou-se descrever os mecanismos da farmacodinâmica dos antibióticos, ressaltando seu mecanismo de resistência e principais eventos adversos, por meio de uma revisão bibliográfica, utilizando livros disponíveis, Google acadêmico, PubMed e Scielo, e dessa forma abrir portas para estudos mais complexos. Após a realização deste trabalho, foi possível perceber que o combate à resistência bacteriana é um problema de saúde pública mundial e deve ser abordado sob vários aspectos, entre as causas para este fenômeno está o uso abusivo e indiscriminado de antibióticos.

terapêutica veio aumentar o arsenal medicamentoso e preencher lacunas existentes no tratamento das doenças infeciosas. Os efeitos nas dinâmicas e nas mobilidades demográficas, sociais e culturais desta complexa inovação científica, médica e farmacêutica continuaram a registar-se até hoje.

Halotolerant bacteria produce a wide range of bioactive compounds with important applications in agriculture for abiotic stress amelioration and plant growth promotion. In the present study, 17 biosynthetic gene clusters (BGCs) were identified in Exiguobacterium profundum PHM11 belonging to saccharides, desmotamide, pseudaminic acid, dipeptide aldehydes, and terpene biosynthetic pathways representing approximately one-sixth of genomes. The terpene biosynthetic pathway was conserved in Exiguobacterium spp. while the E. profundum PHM11 genome confirms the presence of the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway for the isopentenyl diphosphate (IPP) synthesis. Further, 2,877 signal peptides (SPs) were identified using the PrediSi server, out of which 592 proteins were prophesied for the secretion having a transmembrane helix (TMH). In addition, antimicrobial peptides (AMPs) were also identified using BAGEL4. The transcriptome analysis of PHM11 under salt stress reveals the differen...

Departmental sources Background: Calcium dobesilate (CaD) is a member of the synthetic veno-active drug family. Only a small number of reports are available that describe the micro-angiogenic effects of CaD in the current literature. Material/Methods: The antiangiogenic potential of CaD was compared with bevacizumab (Bb), which is a potent angiogenesis inhibitor, in a chick chorioallantoic membrane model. Four different concentrations (10-7 , 10-6 , 10-5 , and 10-4 M) of drug pellet were prepared for each drug. Changes in vessel formation were scored and compared for each drug according to the previous literature. Result: The antiangiogenic behavior of CaD was lower than Bb, despite the significant dose-dependent manner of escalation. The anti-angiogenic scores of CaD were determined as 0.20, 0.47, 0.66, 1.0 in 10-7 , 10-6 , 10-5 , and 10-4 M concentrations, respectively (average score >0.5 was significant). Conclusions: According to the data obtained, this agent should be used carefully for cases in which angiogenesis plays an important role in healing.