CH391L/S13/Metagenomics & Bioprospecting

Introduction & History

Metagenomics and bioprospecting are two 'umbrella' terms that cover many activities within biological research. Both terms are relatively new and were coined in the 1990's. As they both share many of the same activities and techniques, it is possible to confuse these closely related fields. A helpful analogy suggests that metagenomics and bioprospecting are different sides of the same coin. The coin would represent a drive to access the wealth of information and utility that biodiversity has to offer. In this analogy, the difference between basic and applied research approximately delineate the two different sides of the coin as well as the fields which they embody. As a scientific field, metagenomics represents the accumulation of genetic information from a broad range of environmental samples. Conversely, bioprospecting is an application-driven field with the goal of discovering commercially relevant material.

It is acknowledged that bioprospecting is the older of these fraternal fields. Bioprospecting ultimately derived from the field of chemical ecology wherein the discovery and commercialization of natural products was previously known as 'chemical prospecting.' While similar in principle, chemical prospecting employed chemical synthesis of newly discovered, commercially relevant compounds. The advent of next-generation sequencing, recombinant DNA techniques, and biotechnology in general allowed bioprospecting to develop as a unique and separate field. Those same technological advances and interest in natural products would pave the way for metagenomics.

Bioprospecting: Hunting for Utility in Nature

Bioprospecting covers the many activities involved in discovery and utilization of biological material. In the past, bioprospecting has primarily focused upon natural products and drug discovery. Still, bioprospecting has led to the discovery of numerous enzyme and protein tools that are widely used in both the pharmaceutical and research communities. Current research efforts combined with improvements in sequencing technologies may expand the breadth of activities defined as bioprospecting.

Therapeutics & Drug Discovery

There are many examples of bioprospecting geared toward drug discovery. As an outgrowth of chemical prospecting, considerable bioprospecting efforts - both past and present - have centered around plant secondary metabolites. A potent chemotherapy drug, paclitaxel (i.e. taxol) serves as an excellent example of the transition from chemical prospecting to bioprospecting. Discovered in the bark of the Pacific Yew tree, this isoprenoid therapeutic was initially produced through low yield chemical extraction before semi-synthetic production was adopted in 1988 [1]. Using metabolic engineering techniques, researchers created transgenic Arabidopsis thaliana capable of producing taxidene, the first committed step in paclitaxel biosynthesis [2]. Since then, further research has led to plant cell fermentation production. Additional research generated strains of E. coli and yeast containing the metabolic pathways necessary for the production of taxidene and other isoprenoid compounds [1][3]. The tale of paclitaxel is principally considered a feat in the field of metabolic engineering. However, those engineered strains of E. coli and yeast serve as platform technologies for tractable expression of newly discovered enzymes and production of their isoprenoid compounds.

More recently, increasing attention is being paid to marine biodiversity in the search for anticancer therapeutics. Study of tunicated or sea squirts has led to the discovery of numerous cytotoxic compounds with implications for cancer therapies[4]. Commonly known as seaweed, macroalgae present another considerable opportunity for bioprospecting [5].

Research Tools

GFP, polymerases (DNA polymerase to RT), restriction endonucleases

Controversy & Positive Impact

Despite the achievements and promises offered, bioprospecting has raised many ethical and legal debates. BLANK is perhaps one of the most famous examples of this controversy.

Maintenance of biodiversity as a national resource.

Metagenomics: Biological Data Mining

Consideration of biological organization greatly assists understanding the meaning of metagenomics. Within that conceptual framework, metagenomics would be a higher level aspect in genetic hierarchy such as the population or community tiers. Generally, metagenomics refers to the sum of all genetic information present in an environmental sample. The term was coined back in 1998 [6]. Shortly thereafter, researchers characterized the first bacterial rhodopsin, which was isolated from seawater genomic DNA fragments[7]. Since the turn of the century, metagenomics has l

Virology

Many definitions for synthetic biology exist and they continue to evolve. One aspect or definition states that synthetic biology is the application of engineering principles to biological systems. Semantics aside, one must consider the concepts to which these labels are applied.

References

1. Boghigian, Brett A. Simultaneous production and partitioning of heterologous polyketide and isoprenoid natural products in an Escherichia coli two-phase bioprocess. J Ind Microbiol Biotechnol, 2011.

2. Besumbes, Oscar. Metabolic engineering of isoprenoid biosynthesis in Arabidopsis for the production of taxadiene, the first committed precursor of Taxol. Biotechnol Bioeng, 2004.

3. Engels, Benedikt. Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (Paclitaxel) production. Metab Eng, 2008.

4. Rinehart, K.L. Antitumor Compounds from Tunicates. Med Res Rev, 1999.

5. Pereira, Renato C. Bioprospecting for bioactives from seaweeds: potential, obstacles and alternatives. Braz J Pharmacogn, 2012.

6. Handelsman, Jo. Molecular biology access to the chemistry of unknown soil microbes: a new frontier for natural products. Chemistry & Biology, 1998.

7. Beja, Oded. Bacterial Rhodopsin: Evidence for a New Type of Phototrophy in the Sea. Science, 2000.