Heterologous production of bioactive xenoacremone analogs in Aspergillus nidulans / 中国天然药物

Tyrosine-decahydrofluorene derivatives are a class of hybrid compounds that integrate the properties of polyketides and nonribosomal peptides. These compounds feature a [6.5.6] tricarbocyclic core and a para-cyclophane ether moiety in their structures and exhibit anti-tumor and anti-microbial activities. In this study, we constructed the biosynthetic pathway of xenoacremones from Xenoacremonium sinensis ML-31 in the Aspergillus nidulans host, resulting in the identification of four novel tyrosine-decahydrofluorene analogs, xenoacremones I-L (1-4), along with two known analogs, xenoacremones A and B. Remarkably, compounds 3 and 4 contained a 12-membered para-cyclophane ring system, which is unprecedented among tyrosine-decahydrofluorene analogs in X. sinensis. The successful reconstruction of the biosynthetic pathway and the discovery of novel analogs demonstrate the utility of heterologous expression strategy for the generation of structurally diverse natural products with potential biological activities.

The recent advances in developing gene editing and expression tools and the synthesis of natural products in Yarrowia lipolytica / 生物工程学报

Yarrowia lipolytica, as an important oleaginous yeast, has been widely used in metabolic engineering. Y. lipolytica is considered as an ideal host for the production of natural products such as terpenes, polyketides and flavonoids, due to its ability to utilize a variety of hydrophobic substrates, high stress tolerance to acid and salt, high flux of tricarboxylic acid cycle and the ability in providing abundant the common precursor acetyl-CoA. Recently, more and more tools for genetic editing, gene expression and regulation has been developed in Y. lipolytica, which facilitate the metabolic engineering of Y. lipolytica for bio-manufacturing. In this review, we summarized the recent progresses in developing gene expression and natural product synthesis in Y. lipolytica, and also discussed the challenges and possible solutions in heterologous synthesis of natural products in this yeast.

Microbes as a production host to produce natural activecompounds from mushrooms: biosynthetic pathway elucidationand metabolic engineering / 中国天然药物

Mushrooms are abundant in bioactive natural compounds. Due to strict growth conditions and long fermentation-time, microbe as a production host is an alternative and sustainable approach for the production of natural compounds. This review focuses on the biosynthetic pathways of mushroom originated natural compounds and microbes as the production host for the production of the above natural compounds.

Shunt products of aminoansamycins from aas1 overexpressed mutant strain of Streptomyces sp. S35 / 中国天然药物

Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities.

Genome sequence of Streptomyces gilvigriseus MUSC 26T isolated from mangrove forest

Abstract Streptomycetes remain as one of the important sources for bioactive products. Isolated from the mangrove forest, Streptomyces gilvigriseus MUSC 26T was previously characterised as a novel streptomycete. The high quality draft genome of MUSC 26T contained 5,213,277 bp with G + C content of 73.0%. Through genome mining, several gene clusters associated with secondary metabolites production were revealed in the genome of MUSC 26T. These findings call for further investigations into the potential exploitation of the strain for production of pharmaceutically important compounds.

Diversity and communities of culturable endophytic fungi from different tree peonies (geoherbs and non-geoherbs), and their biosynthetic potential analysis

Abstract To know more about the potential roles of endophytic fungi in the formation mechanism of Daodi medicinal material, diversity and communities of culturable endophytic fungi in three types of tree peonies were investigated. Endophytic fungi of three types of tree peonies were isolated and identified. The diversity was analyzed. Bayesian trees constructed by MrBayes 3.2.6 after phylogenetic analysis of the ITS sequences. The endophytic fungi potential for synthesis of natural products was assessed by means of detecting NRPS and PKS gene sequences. In total, 364 endophytic fungi isolates representing 26 genera were recovered from Paeonia ostii 'Feng Dan', Paeonia ostii 'Luoyang Feng Dan', and Paeonia suffruticosa 'Luoyang Hong'. More culturable endophytic fungi appeared in P. suffruticosa 'Luoyang Hong' (206) compared with P. ostii 'Feng Dan' (60) and P. ostii 'Luoyang Feng Dan' (98). The fungal community of P. ostii 'Feng Dan' had the highest richness and diversity. PKSs and NRPS detection rates of endophytic fungi from P. ostii 'Feng Dan' are both the highest among the three types of tree peonies. Results indicate that endophytic fungus is an important factor of Daodi Cortex Moutan forming, and endophytic fungi in peony are related to genuineness of Cortex Moutan.

Selection, isolation, and identification of fungi for bioherbicide production

Abstract Production of a bioherbicide for biological control of weeds requires a series of steps, from selection of a suitable microbial strain to final formulation. Thus, this study aimed to select fungi for production of secondary metabolites with herbicidal activity using biological resources of the Brazilian Pampa biome. Phytopathogenic fungi were isolated from infected tissues of weeds in the Pampa biome. A liquid synthetic culture medium was used for production of metabolites. The phytotoxicity of fungal metabolites was assessed via biological tests using the plant Cucumis sativus L., and the most promising strain was identified by molecular analysis. Thirty-nine fungi were isolated, and 28 presented some phytotoxic symptoms against the target plant. Fungus VP51 belonging to the genus Diaporthe showed the most pronounced herbicidal activity. The Brazilian Pampa biome is a potential resource for the development of new and sustainable chemical compounds for modern agriculture.

Endophytic fungi from medicinal plant Bauhinia forficata: Diversity and biotechnological potential

Bauhinia forficata is native to South America and used with relative success in the folk medicine in Brazil. The diversity, antibacterial activity, and extracellular hydrolytic enzymes of endophytic fungi associated with this plant were studied. Plant samples, which included leaves, sepals, stems, and seeds, were used. Ninety-five endophytic fungal were isolated (18 from leaves, 22 from sepals, 46 from stems, and nine from seeds), comprising 28 species. The most frequently isolated species were Acremonium curvulum (9.5%), Aspergillus ochraceus (7.37%), Gibberella fujikuroi (10.53%), Myrothecium verrucaria (10.53%) and Trichoderma piluliferum (7.37%). Diversity and species richness were higher in stem tissues, and Sorensen’s index of similarity between the tissues was low. Eleven fungi showed antibacterial activity. Aspergillus ochraceus, Gibberella baccata, Penicillium commune, and P. glabrum were those with the greatest antibacterial activity against Staphylococcus aureus and/or Streptococcus pyogenes. Thirteen species showed proteolytic activity, particularly Phoma putaminum. Fourteen species were cellulase positive, particularly the Penicillium species and Myrmecridium schulzeri. All isolates tested were xylanase positive and 10 showed lipolytic activity, especially Penicillium glabrum. It is clear that the endophytic fungi from B. forficata have potential for the production of bioactive compounds and may be a source of new therapeutic agents for the effective treatment of diseases in humans, other animals, and plants. To our knowledge, this is the first study of endophytic fungi from different tissues of B. forficata and their biotechnological potential.

Optimization of Process Parameters for Improved Production of Bioactive Metabolites by Streptomyces tritolerans DAS 165T.

Aims: To optimize the process parameters for enhanced production of bioactive metabolites by Streptomyces tritolerans DAS 165T. Place and Duration of Study: Department of Botany and Microbiology, April 2012 to August 2012. Methodology: Agar well diffusion assay was employed to study the effect of environmental parameters such as incubation period, pH, temperature and salt concentration and influence of various nutrients such as carbon and nitrogen sources and minerals on the bioactive metabolite production by Streptomyces tritolerans DAS 165T.  Results: The production of antimicrobial metabolite was high when the strain was cultured for six days at 35ºC in medium (pH 7.5) with sucrose at the concentration of 2% (carbon source), soya peptone at the concentration of 1% (nitrogen source) and sodium chloride at the concentration of 5%.  Conclusion: This is the first report on the optimization of bioactive metabolite production by Streptomyces tritolerans DAS 165T. As the strain exhibited potent antimicrobial activity, it may be explored for biotechnological purposes.

Optimization of Culture Conditions for Enhanced Antimicrobial Activity of Rhodococcus erythropolis VLK-12 Isolated from South Coast of Andhra Pradesh, India.

Aims: To Isolate and characterize the antimicrobial actinomycetes from the marine habitats of south coast of Andhra Pradesh, India. Place and Duration of the Study: Marine habitats of south coast of Andhra Pradesh, India, between June 2011 and July 2012. Methodology: The soil samples were collected, pre-treated and plated on yeast extractmalt extract dextrose agar medium. Identification of the strain was carried out by employing the polyphasic taxonomical studies including the 16S rRNA sequence based analysis. Phylogenetic tree was constructed using the Molecular Evolutionary Genetic Analysis (MEGA) version 5. The influence of culture conditions and the effect of environmental factors on the biomass and antimicrobial activy\ity of the strain was the focus of this study. Results: A total of 20 actinobacteria were isolated from the marine habitats of south coast of Andhra Pradesh, India, and screened for antimicrobial activity against test bacteria and fungi. The potent bioactive metabolite producing strain was designated as VLK-12. Further polyphasic studies revealed that the Isolate VLK-12 belongs to the genera Rhodococcus. Phylogenetic analysis of 16S rRNA sequencing studies revealed that the strain is closely related to Rhodococcus erythropolis. The crude ethyl acetate extract obtained by culturing the strain on YMD inhibited Gram positive and Gram negative bacteria along with fungi. Conclusion: Rhodococcus erythropolis isolated from the marine habitats of south coast of Andhra Pradesh exhibited antimicrobial activity against pathogens.

Optimization of nutritional and non-nutritional factors involved for production of antimicrobial compounds from Lactobacillus pentosus SJ65 using response surface methodology

Bacteriocins from lactic acid bacteria are ribosomal synthesized antibacterial proteins/ peptides having wide range of applications. Lactobacillus pentosus SJ65, isolated from fermented Uttapam batter (used to prepare south Indian pan cake), produces bacteriocin having a broad spectrum of activity against pathogens. Optimization studies are of utmost important to understand the source of utilization and the conditions to enhance the production of metabolites. In the present study, an attempt was made to identify the parameters involved for maximal production of antimicrobial compounds especially bacteriocin from the isolate L. pentosus SJ65. Initially, optimal conditions, such as incubation period, pH, and temperature were evaluated. Initial screening was done using methodology onevariable-at-a-time (OVAT) for various carbon and nitrogen sources. Further evaluation was carried out statistically using Plackett-Burman design and the variables were analyzed using response surface methodology using central composite design. The optimum media using tryptone or soy peptone, yeast extract, glucose, triammonium citrate, MnSO4, dipotassium hydrogen phosphate and tween 80 produced maximum bacteriocin activity.

Investigación en Química de Productos Naturales en Argentina: Vinculación con la Bioquímica / Development and Research Trends in Chemistry of Natural Products in Argentina: Connection with Biochemistry and Clinical Biochemistry / Pesquisa em Química de Produtos Naturais na Argentina: Vinculagáo com a Bioquímica

En este trabajo se detallan las características y objetivos de la especialidad de Química de Productos Naturales, analizando los conocimientos requeridos de otras especialidades para realizar investigación en la misma. A través de un breve desarrollo histórico se puede observar la vinculación con varias ramas de la Química, como Química Orgánica, Química Biológica y Química Bioanalítica, así como Bioquímica Clínica, entre otras. Se brindan las perspectivas de esta especialidad, mostrando las tendencias en la investigación y en la industria química internacional. El trabajo multidisciplinario se evidencia en las aplicaciones presentadas en investigación.

This article is focused on the characteristics and aims of the Chemistry of Natural Products analyzing the required knowledge from other fields to carry out research. Through a brief historical development, it can be observed that it is related with various branches of Chemistry, including Organic Chemistry, Biological Chemistry and Bioanalytical Chemistry as well as Clinical Biochemistry, among others. Prospects in this field are provided, showing trends in research and in the international chemical industry. A multidisciplinar approach is evident in the research projects shown herein.

Neste trabalho sáo detalhadas as características e objetivos da especialidade de Química de Produtos Naturais, analisando os conhecimentos requeridos de outras especialidades para realizar pesquisa na mesma. Através de um breve desenvolvimento histórico é possível observar a vinculagáo com vários ramos da Química, como Química Orgánica, Química Biológica e Química Bioanalítica, bem como Bioquímica Clínica, dentre outras. Sáo oferecidas as perspectivas desta especialidade, mostrando as tendencias na pesquisa e na indústria química internacional. O trabalho multidisciplinar se evidencia nas aplicagóes apresentadas em pesquisa.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.