Discovery Of Novel Bioactive Compounds Research Articles

Tomophagus cattienensis sp. nov., a new Ganodermataceae species from Vietnam: Evidence from morphology and ITS DNA barcodes

The polypore genus Tomophagus was created to segregate one peculiar species, Ganoderma colossum, from the genus Ganoderma. Recent molecular studies have established the validity of this monotypic genus. Here we report the discovery of a second species of Tomophagus, T. cattienensis sp. nov., from Cat Tien National Park in southern Vietnam, a lowland forest that has been designated as a Biosphere Reserve by the United Nations Educational, Scientific and Cultural Organization (UNESCO). Recognition of this new species is based on combined evidence from morphology, cultural characteristics, and ITS rDNA barcodes. The discovery of this new species may have implications for the discovery of novel bioactive compounds for pharmaceutical use and/or for the pulp industry.

Biodiversity and Chemodiversity: Future Perspectives in Bioprospecting

Biological diversity and its constituent chemical diversity have served as one of the richest sources of bioprospecting leading to the discovery of some of the most important bioactive molecules for mankind. Despite this excellent record, in the recent past, however, bioprospecting of biological resources has met with little success; there has been a perceptible decline in the discovery of novel bioactive compounds. Several arguments have been proposed to explain the current poor success in bioprospecting. Among them, it has been argued that to bioprospect more biodiversity may not necessarily be productive, considering that chemical and functional diversity might not scale with biological diversity. In this paper, we offer a critique on the current perception of biodiversity and chemodiversity and ask to what extent it is relevant in the context of bioprospecting. First, using simple models, we analyze the relation among biodiversity, chemodiversity and functional redundancies in chemical plans of plants and argue that the biological space for exploration might still be wide open. Second, in the context of future bioprospecting, we argue that brute-force high throughput screening approaches alone are insufficient and cost ineffective in realizing bioprospecting success. Therefore, intelligent or non-random approaches to bioprospecting need to be adopted. We review here few examples of such approaches and show how these could be further developed and used in the future to accelerate the pace of discovery.

Exploitation of phage battery in the search for bioactive actinomycetes

Screening of microbial natural products continues to represent an important route to the discovery of novel bioactive compounds for the development of new therapeutic agents, and actinomycetes are still the major producers of biopharmaceuticals. Selective isolation of bioactive actinomycete species, in particular the rare ones, has thus become a target for industrial microbiologists. In this context, bacteriophages have proven to be useful tools as (1) naturally present indicators of under-represented or rare actinomycete taxa in environmental samples, (2) indicators of the relatedness of bioactive taxa in target-directed search and discovery, (3) de-selection agents of unwanted taxa on isolation plates in target-specific search for rare actinomycete taxa, (4) tools in screening assays for specific targets. Against this background, a number of case studies are presented to illustrate the use of bacteriophages as tools in actinomycete-origin bioactive compound search and discovery programs.

Bacteriophages as tools in drug discovery programs

Screening of microbial natural products continues to represent an important route to the discovery of novel bioactive compounds for the development of new therapeutic or other important industrial agents. However, a continuous supply of diverse compounds is needed to meet the needs of industry. Such a supply can only be derived through systematic screening of bioactive compound-producing microorganisms from natural sources.

Natural products with anti-HIV activity from marine organisms.

In order to combat the human immunodeficiency virus (HIV), diverse strategies have been developed to research on compounds which can be developed as therapeutic agents. Screening of natural products derived from numerous species has afforded metabolites with significant antiviral activity against the HIV. The marine environment representing approximately half of the global biodiversity offers an enormous resource for novel compounds. Currently more than 150 natural products with promising levels of anti-HIV activity have been isolated following bioassay guided protocols from aqueous or organic extracts of marine organisms. Some of the most characteristic marinemetabolites that have exhibited significant anti-HIV activity on different biochemical assays designed for chemotherapeutic strategies are: Cyanovirin-N, a protein from a blue green alga; various sulfated polysaccharides extracted from seaweeds (i.e. Nothogenia fastigiata, Aghardhiella tenera); the peptides tachyplesin and polyphemusin, which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus; sponge metabolites such as avarol, avarone, ilimaquinone and several phloroglucinols; and a number of metabolites from marine fungi such as equisetin, phomasetin and integric acid. Considering that number of unique metabolites that have been isolated from a small extent of the ocean's biological and chemical diversity, the oceans represent a virtually untapped resource for the discovery of novel bioactive compounds.

Isolation of new actinomycete strains for the screening of new bioactive compounds.

In order to facilitate the discovery of novel bioactive compounds from microorganisms, various techniques for isolation of new actinomycete strains have been attempted. Studies of the vertical distribution of actinomycetes in soil, isolation of actinomycetes from desert soils or fallen leaves, selective isolation of Kitasatospora strains using novobiocin or Actinoplanes strains using the chemotactic method, and the use of gellan gum as a solidifying agent were carried out. We discovered 9 novel bioactive compounds from actinomycete strains isolated under unusual conditions, and proposed two new genera, five new species and one new subspecies.

Investigation of actinomycete diversity in the tropical rainforests of Singapore

Five thousand actinomycetes were isolated from soil samples collected from rainforests in Singapore and the generic identities of these isolates were determined by using a procedure that combined morphological, chemotaxonomic and 16S rDNA sequence-based phylogenetic analyses. Actinomycetes belonging to a total of 36 genera were identified. The most abundant isolates are members of Streptomyces, Micromonospora, Actinoplanes, Actinomadura, Nonomuria, Nocardia and Streptosporangium. By phylogenetic analysis of 16S rDNA sequences of our isolates together with those of known actinomycete species, we also evaluated the species diversity of several genera including Streptomyces, Micromonospora, Nonomuria, and Actinomadura. We found that: first, the tropical isolates are present in most clades represented by known species; and second, many tropical isolates form new clades distant from the known species, indicating the presence of unidentified taxa at both species and genus levels. Based on these results, we conclude that actinomycete diversity in the tropical rainforest is very great and should represent an excellent source for discovery of novel bioactive compounds.