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ACCESSING AUSTRALIAN BIODIVERSITY. D. I. KURTBOKE and H. G. WILDMAN AMRAD Discovery Technologies Pty. Ltd., 576 Swan Street, Richmond, Melbourne, Victoria 3121, Australia
Code Number:AC98002 ABSTRACT. The screening of microbial natural products continues to represent an important route to the discovery of novel chemicals for development of new therapeutic agents, and evaluation of the potential of lesser-known and/or new bacterial taxa is of increasing interest. AMRAD Discovery Technologies Pty. Ltd. is committed to the discovery of novel biologically active molecules from microorganisms isolated from Australian environmental samples as leads for the development of new compounds for the treatment of major human diseases. Australia is one of the world's most biodiverse countries. It has been geologically separated from the main continents for over 20 million years, which has allowed a period of extensive evolutionary divergence. As a result, Australia has a very high rate of endemism in both its flora and fauna. The Australian continent contains a diverse range of biogeographic regions: for example, an arid interior, tropical monsoon areas in the north, Mediterranean and temperate climates in the south, alpine regions in Tasmania and in the Southeast. Australian marine environments are probably the most biodiverse in the world. It is one of the largest countries with most latitudinally diverse marine environments. Exposed to three major ocean currents, the marine environment of Australia ranges from extensive coral reefs, to seagrass plains, giant kelp forests and sand-bottomed habitats and, furthermore, its external territories extend to Antarctic and sub-Antarctic waters. Stretching from the tropics to the Antarctic, Australia's terrestrial and marine environments provide diverse habitats for a unique range of flora and fauna which has been poorly investigated for the presence of pharmaceutical-active compounds. There is therefore an exciting opportunity within Australia to make important contributions in the field of drug discovery through the acquisition and screening of this biota.
AMRAD Discovery Technologies Pty. Ltd. (ADT; formerly known as AMRAD Natural Products Pty. Ltd.) was established to investigate Australian biodiversity for pharmaceutical purposes. The objective of the company is to discover novel, pharmaceutically-active lead compounds for development as new medicines either by ADT alone or in collaboration with other pharmaceutical companies, through the screening of forge libraries of natural product extracts and synthetic chemical samples against biological targets of relevance to major human diseases. Accessing the biodiversity of the entire Australian continent which is large, diverse, very endemic, largely "unscreened" and strategically positioned with respect to other regions of high biodiversity in South East Asia, provides a strategic-edge to ADT in natural products sample collection. Filamentous bacteria, mostly actinomycetes, comprise an integral part of ADT's isolation program. Since the discovery of streptomycin from Streptomyces griseus in 1944, actinomycetes, and in particular streptomycetes, have been the greatest source of antibiotics, producing about two thirds of the 9000 or so naturally occurring compounds isolated to date. Most antibiotics and other useful secondary metabolites from the aforementioned genus have been well studied, identified and applied in industry. Therefore, the search for novel compounds is now concentrated on rarely isolated actinomycetes. Very little is known about the endemism of the Australian microbial communities. It has been estimated that so far <1% of all microorganisms existing have been identified and characterized. Taxonomic relationships between microbes are still lacking and only a minor proportion of microbes in natural environments has been isolated by conventional methods. ADT is now developing effective isolation procedures through focusing principally on Australia's unique habitats and microenvironments. ADT obtains numerous environmental source samples each year to support its drug discovery programs, which has the capacity to conduct in excess of 1 million primary screening events per year. As well as running its own in- house isolation program, ADT has formed arrangements with relevant institutes, organizations and authorities, e.g. the Antarctic Cooperative Research Center (CRC) in Tasmania and the Australian Institute of Marine Science (AIMS) in northern Queensland, to secure access to the extensive biodiversity of Australia and South East Asia. In both institutes specialists in marine and psychrophilic and -trophic microbiology are developing highly selective isolation protocols for the detection and isolation of novel genera of actinomycetes for pharmaceutical screening, thus increasing the likelihood of finding "talented" actinomycetes in Australian environments. Highly selective isolation protocols used in ADT include the use of specific actino- or bacteriophage to selectively eliminate unwanted species from isolation plates and to allow selection of rare actinomycetes, which would otherwise go undetected. These techniques are applied to the samples collected from extreme habitats such as samples of marine invertebrates, sediments, tropical rain forest litter, Northern Territory desert soils or Antarctic soils. Antarctica is an extremely diverse environment, which includes freshwater lakes, hypersaline lakes and a variety of soil habitats. Microorganisms living in these environments have, therefore, had to adapt to these harsh and changeable conditions and thus represent an exciting pool of novel biodiversity. Actinomycetes have been isolated previously from Antarctic environments such as from sulphurcones, the proximity of glaciers, and soils along the shores of ponds. However, most of these actinomycetes were from the genus Streptomyces. Using highly selective isolation techniques, scientists at ADT together with the specialists at the CRC have isolated rare actinomycetes from several Antarctic soils and mosses. Preliminary morphological and molecular identification suggests that several of these strains are novel. Actinomycetes have also been isolated from marine environments such as sediments, water column samples and marine macroorganisms using dry heat and selective inhibitors like nalidixic acid (Nonomura & Hayakawa, 1988). Selective protocols revealed the occurrence of non-streptomycete actinomycetes such as actinoplanetes (Fig. 1), maduromycetes, nocardioforms (Fig. 2) and actinobacteria in near and offshore marine sediments.
Figure 1. An Actinoplanes sp. isolated from near shore marine sediments. Figure 2. Rhodococcus sp. isolated from near shore marine sediments.
Figure 4. Planobispora sp. isolated from desert soils of Australian Northern Territory. Figure 5. Geodermatophilus sp. isolated from desert soils of Australian Northern Territory.
The combination of in-house expertise with skills available in our collaborating institutes is helping to create a unique microbial collection at ADT. Highly selective isolation protocols reveal the presence of rare actinomycetes in Australian environments and contribute to global microbial ecological knowledge. ACKNOWLEDGEMENT. We thank Dr. M. Tait (Director of Natural Product Screening) and Dr. N. Gough (General Manager of ADT) for their support and encouragement. REFERENCES Nonomura, H. & M. Hayakawa (1988). New methods for the selective isolation of soil actinomycetes. In: Y. Okami, T. Beppu & H. Ogawara (eds.) Biology of Actinomycetes '88. Japan Scientific Societies Press, Tokyo. Kurtboke, D. I., N. E. Murphy & K. Sivasithamparam (1993). Use of bacteriophage for the selective isolation of thermophilic actinomycetes from composted eucalyptus bark. Can. J. Microbiol., 39: 46-51 Williams, N. J. (1997). The detection, isolation and identification of rare actinomycetes. Abstract ISBA '97. Beijing, China. Copyright 1998 C.E.T.A., The International Centre for Theoretical and Applied Ecology, Gorizia The following images related to this document are available:Photo images[ac98002b.jpg] [ac98002c.jpg] [ac98002a.jpg] [ac98002d.jpg] [ac98002e.jpg] |
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