7. TENDENCIA DE SUPERVIVENCIA DE LOS HEDGE FUNDS
7.1 Revisión de Literatura
The metagenomic analysis led to the identification and characterization of many novel biocatalysts and drugs.21 The analysis of soil metagenomes revealed many more antibiotics and mechanisms of antibiotic resistance than found in cultivation-based techniques thus far.24
The screening for bleomycin resistance genes of a metagenomic DNA library of activated sludge revealed two different genes that showed no similarity to the genes of bleomycin-producing Actinomycetes or clinical isolates.134 The antibiotic bleomycin was firstly identified in Streptomyces verticillus and used as an antitumor agent.135,136 However, bleomycin-producing Actinomycetes harbor resistance genes (ble) that code for bleomycin resistance proteins (BRPs), sequestering the antibiotic to pre-vent DNA cleavage.136 It was proved that this resistance mechanism spread over to bacteria of clinical isolates that normally do not produce bleomycin.137−139 Recently, a novel antibiotic — palmitoylputrescine — was found in bromeliad tank water and a new mechanism of tetracycline
inactivation was found in the oral metagenome.21,25,140Thus, non-clinical environments provide a huge potential to discover new antibiotics, as well as resistance mechanisms that may lead to new developments in drug research, extending the range of effective pharmaceuticals against infec-tious diseases.21,134
Nonetheless, most pharmaceutical companies focus on new drugs against long-term chronic diseases such as obesity or high cholesterol, in comparison to the economically unfavorable discovery of novel antibiotics that are essential to overcome the “global antibiotic resistance problem.”142 However, it should not be overseen that natural products from bacteria or fungi constituted of 63 percent of all newly used anti-infectives between 1983 and 1994.143
Biosynthetic pathways accessed by metagenomic studies are mostly involved in vitamin biosynthesis. Clones harboring genes that encode 2,5-diketo-D-gluconic acid reductase, which produces vitamin C out of glu-cose, have been detected in metagenomic libraries derived from enrichment cultures.116,144
Prokaryotes also play a key role in environmental bioremediation, since they are able to degrade all naturally occurring compounds and most xenobiotics.21 However, genes that are necessary for remediation are different in culture from those found in the natural occurring envi-ronmental bioremediation. Therefore, metagenomics reveals insights into diverse xenobiotic degradation pathways of natural environments that may be important in cleaning up oil spills, groundwater, sewage or nuclear waste in order to restore healthy ecosystems.1,145,146
The industry primarily focuses on prokaryotic metagenomes, since prokaryotes show maximal biodiversity and their genomes can easily be targeted by conventional screening applications.9 In contrast, eukaryotes have only infrequently been used for metagenomic research. This is due to their large genomes that are associated with high sequencing costs and their high proportion of DNA that does not code for proteins. With the develop-ment of higher-throughput sequencing technologies and decreasing costs, eukaryotes should come more into the focus of metagenomic research.8 The chemical and pharmaceutical industries mainly switched established conventional chemical processes to biotechnological areas that require metagenomic research in order to discover new enzymes, biocatalysts and
Biodiversity and Metagenomics 59
applications.9 In addition to the discovery of new enzyme classes, vari-ations in functional properties within the classes are also important for biotechnology. Consequently, enzymes that function under specific condi-tions such as higher temperature, pH extremes or elevated salinity levels at the center of interest.21 As an example, a novel thermostable esterase was identified with a pH range of 5.5–7.5 and an extremely wide temperature range with an optimum at 47◦C.147 Further key features of an ideal bio-catalyst include activity, stability, specificity and efficiency. In addition, the novel enzyme should contain a single backbone with superior functionality and an entirely new sequence to prevent competing property rights. Finally, the heterologous expression of new enzymes should generate adequate pure protein in appropriate amounts at reasonable costs.9
6. CONCLUSION
The discovery of microbes in the seventeenth century marked the begin-ning of modern microbiology. Since then, humankind has benefited enor-mously from the study of cultivated microorganisms that represent only a miniscule fraction of microbes actually present on earth. In the past decades, we have realized the importance of microbial communities. We have expanded our knowledge of evolution, biodiversity, and ecology that has led to major advances in medicine, agriculture, energy production and bioremediation. The study of genetic and genomic information from envi-ronmental communities all over the world without prior cultivation as provided by metagenomics currently reveals new insights into the micro-bial community, reshaping the landscape of microbiology and revealing the secrets of the uncultured world.1
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