Earth Sciences Division (ESD) Department of Energy (DOE) Lawrence Berkeley National Laboratory (LBNL)

Bioprospecting

Bioprospecting is the continuous search for “old” and “new” microorganisms with novel, untapped genetic traits to advance science, preserve a sustainable genetic pool, and fairly and meaningfully commercialize microbial products by industry to benefit humankind. Some say, no monetary value can be placed on the worth of microbial diversity since the very existence of life is dependent on microorganisms. Others think, the true value of microbial diversity includes not only the diversity with respect to species richness but also the direct and indirect economic value of profits resulting from commercialization of microbial metabolic products and processes.

COP 11Ever since the “Earth Summit” in 1992 in Rio de Janeiro, science and industry have a changed view of biological diversity and bioprospecting. With the Convention on Biodiversity (CBD) the world now has an international, legally binding treaty for conservation of biological diversity; sustainable use of its components, and fair and equitable sharing of benefits arising from genetic resources. Follow-up and related agreements and protocols such as the Cartagena Protocol (2000), the Nagoya Protocol (2010), and the UN-declared Decade of Biodiversity (2011-2020) have further strengthened the commitment of signatory countries to the spirit of CBD.

The upcoming Conference of Parties (COP 11) in Hyderabad, India in 2012 will be preceded by “Worldwide Views On Biodiversity” citizens consultations on September 15, 2012.

Worldwide sites of citizen consultation
Worldwide sites of citizens consultation planned for September 15, 2012.

Carl Woese wrote in 2002: “Where there is life, there are microbes.” In this spirit, the main research interest of my laboratory is microbial diversity in extreme environments. We apply a polyphasic approach, i.e., a complementary set of microbial physiology, chemical taxonomy, and non-culture-based methods to assess and monitor microbial communities. While we use pattern recognition techniques, such as electrophoretic karyotyping and signature lipid biomarker analysis, as well as genomic sequencing to survey and characterize selected microbial assemblages, we also very much rely on developing new isolation and cultivation techniques. Newly isolated microorganisms are then screened in collaboration with partners in academia and industry for novel traits and natural products.

Over the past 17 years, my laboratory has participated in the US-DOE/NNSA Global Initiatives for Proliferation Prevention (GIPP) program. The projects opened new, often once-in-a-lifetime opportunities for environmental sample collection. The “Search for Ancient Microorganisms in Lake Baikal” project targeted the microbial diversity present in and around Lake Baikal, the oldest and deepest continental lake in the world in south central Siberia. We collected the first non-costal water and soil samples from the Lake and from the surrounding hot springs. We also participated in two expeditions of the international Baikal Drilling Project (www.geol.sc.edu/SIL/bdp.htm). Over 2,200 strains were isolated, preserved, and identified based on biochemical tests, whole-cell fatty acid methyl ester (FAME) analysis, genomic DNA fingerprinting, electron microscopic cell morphology and fine structure, and restriction enzyme profiles.

In other projects, such as the “Microbially Derived Agricultural Crop Protection Products”, “Screening of Botanical and Microbial Species Collected within the Territory of the Former Soviet Union for Pharmaceutical and Agrochemical Activities”, “Microbial Diversity for Novel Biotechnology Applications”, and “Novel Enabling Technologies for Gene Isolation and Transfer”, we developed multi-year programs for systematic seasonal collection of microbial diversity in selected extreme environments in Chernobyl, Ukraine, the Siberian permafrost, on the Kamchatka peninsula, the Caucasus Mountain and the high salinity soils in Georgia, and the deserts of Uzbekistan. We leveraged our microbial physiology expertise and proprietary fermentation methods and benefited from high-throughput assays of the industry partners (American Home Products, DuPont, Diversa, and Pioneer-HiBred International) to screen thousands of microbial organisms, plant extracts, and filamentous fungi collected. Novel microbial natural products with agricultural and biomedical applications were discovered. In still ongoing industry collaboration, dozens of antifungal peptides and insecticidal molecules have been discovered and patented. The transgenic plants of major crop plants generated now express extremophilic microbial sequences.

More recently, we have expanded our interest in microbial diversity to probiotics and their application in neonatal development and autoimmune diseases of the GI system, to molecular level monitoring of pathogens and select agents and novel anti-TB, antifungal, and antiviral drug design. With our colleagues in the US and abroad and with new industry partners, such as Novici Biotech, New Horizons Diagnostic, and Royal DSM, we are pursuing projects that equally benefit science and industry.

Of the many spin-off ideas that have resulted from past and current bioprospecting-based projects, let’s only mention a few: (1) a NATO Collaborative Linkage Grant provided seed money for a feasibility study to introduce sequences from hyperthermophilic microorganisms into legumes for post-harvest modification through heat activation of enzymes of interest during storage. (2) In a Civilian Research and Development Foundation (CRDF)-funded project, we joined forces with institutes in Armenia, Azerbaijan, and Georgia and established a network of microbial culture collections as biotechnology resources. (3) In Azerbaijan, a collaborative investigation funded by CRDF and the local National Academy of Sciences collected petroleum hydrocarbon degrading and biosurfactants expressing microorganisms to cleanup oil contaminated environments. (4) With colleagues in Japan, we genetically engineered fungi that produce high efficiency lignocellulolytic enzymes for biomass-to-biofuels applications.

Microorganisms, especially extremophiles, produce unique biocatalysts and natural products that function under extreme conditions comparable to those prevailing in various industrial processes. Rational bioprospecting has elevated the search for microorganisms with novel capabilities to a safe, ethical, and meaningful conduct that equally benefits science and industry. Thus, bioprospecting provides science with the opportunity to understand microbial diversity for it is the microorganisms that are the foundation of the biosphere on our planet.

Current projects and collaborators

Microbially derived crop protection products (collaborator: Pioneer HiBred International, a DuPont Company)

The role of bacteriophages in the biology of sulfate-reducing bacteria (science lead: Romy Chakraborty; collaborators: Eliava Institute of Bacteriophage, Microbiology, and Virology, Tbilisi, Georgia and New Horizons Diagnostics)

Targeted enzyme discovery (science lead: Steven Singer; collaborators: Durmishidze Institute of Biochemistry and Biotechnology, Tbilisi, Georgia and Novici Biotech)

Novel enabling technologies for gene isolation and transfer (collaborator: Ukrainian Anti-Plague Research Institute, Odesa, Ukraine, Institute of Cell Biology and Genetic Engineering, Kyiv, Ukraine, and Pioneer HiBred International, a DuPont Company)

Probiotics that specifically grow on milk oligosaccharides (science lead: David Mills, UC Davis; collaborators: National Center for Disease Control, Tbilisi, Georgia, ArmBiotech, Yerevan, Armenia, and Royal DSM)

Genotyping Yersinia pestis in Central Asia (science lead: Ping Hu; collaborators: National Center for Disease Control, Tbilisi, Georgia, Institute of Biotechnology, Bishkek, Kyrgyzstan, and State Sanitary Epidemiological Surveillance Services, Dushanbe, Tajikistan)

Soil anthrax foci in Kazakhstan (science lead: Jason Blackburn, University of Florida; collaborator: Research Institute for Biological Safety Problems, Gvardeiski, Kazakhstan)

Effect of probiotics on familiar Mediterranean fever patients (collaborator: Institute of Biochemistry, Yerevan, Armenia)

Development of an anti-influenza model using QSAR (collaborators: Ukrainian Anti-Plague Research Institute, Odesa, Ukraine, Physico-Chemical Institute, Odesa, Ukraine, Kansas City Plant, and Research International, Inc.)

Screening of anti-virus activity of indol-containing tetracyclic condensed systems (collaborators: Eliava Institute of Bacteriophage, Microbiology, and Virology, Tbilisi, Georgia, Kansas City Plant, and Research International, Inc.)