180
polymerase PARP, destruction of lamin B, and also fragmentation of genomic DNA
(Zhou et al. 2003). Intrinsic mode of apoptosis with role played by p38 MAPK was
found in ARO and KAT-4 cells (She et al. 2006).
7.4
Metagenomics: A Tool to Uncover Novel Anticancer
Drugs
Microbial dynasty has been a never-ending treasure house of various biologically
active compounds. Even as researchers try to understand more about microbes and
their various attributes, the horizon of microbial dynasty seem to be nowhere in
sight. Microbes have always been the reservoir for discovery for many types of
anticancer drugs that went onto gain clinical and commercial importance. In the
past decades, the contribution made by cultured microbes to the list of anticancer
therapeutic agents has been enormous and many of them have found way into clinical use. Some of these that were effective as cancer chemotherapeutic drugs are
doxorubicin hydrochloride, bleomycin, daunorubicin, and mitomycin (Pettit 2004).
On the other hand, there are new problems in cancer therapy like multidrug resistance cancers, outbreaks of new diseases, and increasing cases of cancer incidences,
both in developing and developed countries. The above-mentioned scenario places
an enormous weight on the scientific community to explore newer techniques to
discover novel potential anticancer molecules that could be the solution to various
problems related to cancer treatment.
In this respect, research has come out with a molecular biology tool that helps in
exploring the treasure of secondary metabolites of uncultured microbes through
metagenomic approach. Research across globe came to the convincing conclusion
that the uncultured microbial counterpart weighed more in number than the cultivable ones (Pace et al. 1985). Metagenomics involve isolation of DNA from the
source sample of any origin and then delivery of the DNA into host bacteria with the
help of an appropriate vector. These libraries can be screened for presence of specific antibiotic or enzyme-encoding genes (Schloss and Handelsman 2003). The
tool will help in uncovering therapeutic compounds that will be more efficient than
the compounds that are in clinical use presently. Polyketides are the most wellknown cluster of genes that encode for production of a variety of secondary metabolites, especially antibiotics and those with antitumor properties. Due to the
importance of polyketide-gene family in drug discovery from microbes, metagenomic searches has mostly concentrated on hunting natural compounds in metagenomic libraries from these gene clusters. Polyketides offers a diverse group of
secondary metabolites, showcasing diversity both in terms of their structure and
function. Polyketide-based compounds are known to possess pharmacologically
diverse group of functions that include antimicrobial, antifungal, antiparasitic, antitumor, and agrochemical properties. The large spectrum of functional use of
polyketide family of compounds keeps them as economically important, clinically
significant, and of high commercial value in Industrial aspect (Cheng et al. 2003).
The discovery of new antibiotics, Turbomycin and its variants from a soil
metagenomic library, showed that the potential lies with the tool in discovering
V.M. Dan and R. Sanawar
polymerase PARP, destruction of lamin B, and also fragmentation of genomic DNA
(Zhou et al. 2003). Intrinsic mode of apoptosis with role played by p38 MAPK was
found in ARO and KAT-4 cells (She et al. 2006).
7.4
Metagenomics: A Tool to Uncover Novel Anticancer
Drugs
Microbial dynasty has been a never-ending treasure house of various biologically
active compounds. Even as researchers try to understand more about microbes and
their various attributes, the horizon of microbial dynasty seem to be nowhere in
sight. Microbes have always been the reservoir for discovery for many types of
anticancer drugs that went onto gain clinical and commercial importance. In the
past decades, the contribution made by cultured microbes to the list of anticancer
therapeutic agents has been enormous and many of them have found way into clinical use. Some of these that were effective as cancer chemotherapeutic drugs are
doxorubicin hydrochloride, bleomycin, daunorubicin, and mitomycin (Pettit 2004).
On the other hand, there are new problems in cancer therapy like multidrug resistance cancers, outbreaks of new diseases, and increasing cases of cancer incidences,
both in developing and developed countries. The above-mentioned scenario places
an enormous weight on the scientific community to explore newer techniques to
discover novel potential anticancer molecules that could be the solution to various
problems related to cancer treatment.
In this respect, research has come out with a molecular biology tool that helps in
exploring the treasure of secondary metabolites of uncultured microbes through
metagenomic approach. Research across globe came to the convincing conclusion
that the uncultured microbial counterpart weighed more in number than the cultivable ones (Pace et al. 1985). Metagenomics involve isolation of DNA from the
source sample of any origin and then delivery of the DNA into host bacteria with the
help of an appropriate vector. These libraries can be screened for presence of specific antibiotic or enzyme-encoding genes (Schloss and Handelsman 2003). The
tool will help in uncovering therapeutic compounds that will be more efficient than
the compounds that are in clinical use presently. Polyketides are the most wellknown cluster of genes that encode for production of a variety of secondary metabolites, especially antibiotics and those with antitumor properties. Due to the
importance of polyketide-gene family in drug discovery from microbes, metagenomic searches has mostly concentrated on hunting natural compounds in metagenomic libraries from these gene clusters. Polyketides offers a diverse group of
secondary metabolites, showcasing diversity both in terms of their structure and
function. Polyketide-based compounds are known to possess pharmacologically
diverse group of functions that include antimicrobial, antifungal, antiparasitic, antitumor, and agrochemical properties. The large spectrum of functional use of
polyketide family of compounds keeps them as economically important, clinically
significant, and of high commercial value in Industrial aspect (Cheng et al. 2003).
The discovery of new antibiotics, Turbomycin and its variants from a soil
metagenomic library, showed that the potential lies with the tool in discovering
V.M. Dan and R. Sanawar