Taxonomy-guided microbial biodiscovery

finding the low-hanging fruit

Research output: Chapter in Book/Report/Conference proceedingConference abstract

Abstract

The microbial world has long been a happy hunting ground for biologically active small molecules and has given rise to countless blockbuster pharmaceuticals such as vancomycin, lovastatin and ivermectin. However, with much of the molecular "low-hanging fruit" having already been picked over the past five decades, it is becoming increasingly difficult to find truly novel bioactive scaffolds from microbes. In recent years, a variety of different approaches have been explored to improve the chances of identifying novel microbial metabolites, including isolating microbes from unusual or extreme environments, cultivating previously unculturable microbes or attempting to unlock silent microbial metabolites through co-cultivation or epigenetic modification.
Recently, we have been exploring an alternative approach combining classical taxonomy, chemotaxonomy and total genome mining to rapidly identify high-priority “talented” strains from larger collections of microorganisms. Using this approach, we have identified 12 putative novel species of Aspergillus from a library of ~200 isolates collected during a survey of forest and scrub soils in the South Burnett Region of Queensland. Preparative-scale cultivation of these 12 organisms led to the isolation of over 180 metabolites, of which more than 60 (>33%) were novel. In our experience, this is a much higher hit rate than is typically observed through traditional unguided or bioassay-guided biodiscovery approaches.
This presentation will focus on the chemotype of one of these new species – Aspergillus burnettii – which was isolated from arable soil collected at Coalstoun Lakes that had previously been under peanut cultivation. When grown on pearl barley, A. burnettii produced in excess of 50 secondary metabolites, including a novel family of pentaene polyketides, named the burnettienes, a novel family of polyketide tetramic acids, named the burnettramic acids, as well as the previously reported compounds, nominine, asperlicin E, hirsutide, (+)-kotanin, (+)-isokotanins A–C, , paspaline, 14-hydroxypaspaline and ochratoxin A. The compounds were screened for activity against a panel of bacteria, fungi, protozoa and mammalian cells. Most notably, the burnettramic acids showed potent antifungal in vitro activities against Candida albicans and Saccharomyces cerevisiae.
Original languageEnglish
Title of host publicationOrganic18 RACI Organic Division National Conference
Subtitle of host publicationconference program
PublisherRoyal Australian Chemical Institute
Pages50
Number of pages1
Publication statusPublished - 2018
EventOrganic18: RACI Organic Division National Conference - The University of Western Australia, Perth, Australia
Duration: 2 Dec 20186 Dec 2018
http://www.organic18.com.au/

Conference

ConferenceOrganic18
CountryAustralia
CityPerth
Period2/12/186/12/18
Internet address

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  • Cite this

    Piggott, A. M. (2018). Taxonomy-guided microbial biodiscovery: finding the low-hanging fruit. In Organic18 RACI Organic Division National Conference: conference program (pp. 50). Royal Australian Chemical Institute.