Biodiscovery Opportunities from Actinobacteria of Extreme Environments Alan T. Bull

41 Pages·2014·1.43 MB·English

BIOTA-FAPESP Workshop: Thinking Big about Small
Beings: Recent Advances on Microbial Diversity,
Ecology and Biodiscovery
São Paulo, Brazil. April 28-29, 2014

Biodiscovery Opportunities from

Actinobacteria of Extreme Environments

Alan T. Bull

  

School of Biosciences
University of Kent, Canterbury, UK.
Inspired by Brazilian Biodiversity
Alfred Russel WALLACE Charles DARWIN
1823 – 1913 1809 – 1892
Outline
• Some misconceptions – a personal view
• Search and Discovery philosophy
• Bioprospecting the Extremobiosphere
• Sampling campaigns
• Screening options
• What we have so far:
1. Deep-sea discoveries
2. Hyper-arid-desert discoveries
• In Conclusion:
1. Cautions and Lessons
2. Some basic research objectives
Misconceptions that obstruct natural product
search and discovery

1. Microbial systematics and the search for natural products is
simply stamp collecting.

2. Natural products are exhausted.

3. Combinatorial chemistry provides superior drug candidates
than natural products.

4. Isolation and characterization of natural products is
laborious and slow.

5. Natural products pose too great a synthetic challenge.
Factors Stimulating Natural Product Search
and Discovery
In the search for new therapeutic drugs there is an urgent need to discover
new chemical scaffolds.

• Biologically relevant chemistry: products of adaptive evolution

• Pre-validated chemistry: synthesized by proteins to interact with
proteins (and other biomolecules)

• Privileged chemical scaffolds: structures that provide selective
ligands for a range of biological targets

• Combinatorial chemistry: large investments, poor returns

• Microbial superdiversity: exploring microbial dark matter
Microbial Dark Matter
• Single cell genomics
• Diverse sampling sites
• 201 Uncultivated Bacteria and
Archaea sequenced
• 29 underrepresented or unknown
lineages
• A small data set producing an 11%
increase of known microbial
phylogenetic diversity
• Two new Superphyla defined
– DPANN archaea
– Patescibacteria

Rinke, C. et al. (2013) Nature 499: 431.
How to Maximise Biodiscovery Success:
Focus on Poorly Explored SPACE
• Taxonomic space

• Chemical space

• Environmental space

• Biological target space

• Genome space
Taxonomic Space: The Focus on
Actinobacteria
• Traditionally regarded as
soil and freshwater bacteria
but now reported in all
extreme environments on a
global scale.

• Exceptional capacity to
produce compounds having
a wide range of
bioactivities; “gifted
genera”.

• Very large Phylum of
bacteria with new taxa
being discovered at a high
rate.
2007-2013: 3 Novel families, 20 Novel genera,
Marine-derived actinomycetes
Subramani, R., Aalbersberg,W. (2013) Appl. Microbiol. Biotechnol. 97: 9291-9321.
Environmental Space
Extreme Novel Natural
Novel Organisms
Environments Products
“Bacteria dwell in virtually every spot that can sustain any sort of
life. And we have underestimated their global number
because we, as members of a Kingdom far more restricted in
potential habitation, never appreciated the full range of places
that might be searched.”

Stephen Jay Gould (1996) Planet of the bacteria, Washington Post Horizon.