Genome Min
531
Part C | 21.1
21. Genome Mining for Bioactive Compounds
Soumya Haldar, Kalpana H. Mody
Coral reef environments are a rich source of biologically active natural products. However, due
to their vulnerable nature and stringent environmental laws, it is always difficult to explore
such environments physically. With the advent
of molecular biology, many new strategies have
evolved for the discovery of novel natural bioproducts from sensitive marine environments. Analyses
of plant and microbial genome sequences have
revealed many genes and gene clusters encoding
proteins similar to those known to be involved in
the biosynthesis of structurally complex natural
products. The concept of genome mining evolved
from this concept, where large-scale deoxyribonucleic acid (DNA) sequencing approaches have
been used. Basically, this strategy involves two
approaches: sequence-based metagenomics and
functional metagenomics. Although many breakthroughs have been achieved, presently, the global
pharmaceutical pipeline consists of few approved
drugs and a large number of marine chemicals in
different stages of preclinical trials. It is anticipated
that with the advent of new molecular techniques,
the metagenomics approach will be more useful
for the discovery of natural bioactive compounds.
21.1 Overview ............................................. 531
21.2 Temporary Halt in the Discovery
of Bioactive Compounds....................... 533
21.3 Future Directions ................................. 533
21.3.1 Genome Mining ........................ 533
21.3.2 Functional Metagenomics .......... 534
21.3.3 Phenotypic Detection
of the Desired Activity................ 534
21.3.4 Induced Gene Expression ........... 535
21.3.5 Sequence-Based Metagenomics . 536
21.4 The Hurdles of Drug Discovery .............. 536
21.5 Marine Pharmaceuticals
Under Clinical Trials ............................. 536
References................................................... 538
In the present chapter, an attempt has been made
to gather detailed information on the present status of coral-derived bioactive compounds and on
the reasons for momentary halt in biodiscovery
of marine natural products, and to outline future
prospects of research on marine/coral associated
bioactive compounds.
21.1 Overview
Marine organisms contain many potential novel bioactive compounds because of the unique environmental
conditions (high ionic strengths, low level of light, cold
or warm temperatures, and pressure) prevailing in their
habitats. Several groups of marine organisms, including soft-bodied sessile invertebrates, such as tunicates,
soft corals, and certain sponges, appear defenceless yet
they produce bioactive compounds to protect themselves from predators. These organisms are rich in
nutritionally important substances and use an arsenal
of chemical defences and chemical repellents to protect
themselves when competing for space. The incidence of
predation is low because of the production of toxic compounds and the possession of some form of calcareous
sclerites. The abundance and diversity of natural products having potential biological activities have provided
scientists with the opportunity to discover new drugs.
In the recent past, bioprospecting of new marine natural products (NMNP) has resulted in the discovery of
several thousand novel molecules. The rich biodiversity
531
Part C | 21.1
21. Genome Mining for Bioactive Compounds
Soumya Haldar, Kalpana H. Mody
Coral reef environments are a rich source of biologically active natural products. However, due
to their vulnerable nature and stringent environmental laws, it is always difficult to explore
such environments physically. With the advent
of molecular biology, many new strategies have
evolved for the discovery of novel natural bioproducts from sensitive marine environments. Analyses
of plant and microbial genome sequences have
revealed many genes and gene clusters encoding
proteins similar to those known to be involved in
the biosynthesis of structurally complex natural
products. The concept of genome mining evolved
from this concept, where large-scale deoxyribonucleic acid (DNA) sequencing approaches have
been used. Basically, this strategy involves two
approaches: sequence-based metagenomics and
functional metagenomics. Although many breakthroughs have been achieved, presently, the global
pharmaceutical pipeline consists of few approved
drugs and a large number of marine chemicals in
different stages of preclinical trials. It is anticipated
that with the advent of new molecular techniques,
the metagenomics approach will be more useful
for the discovery of natural bioactive compounds.
21.1 Overview ............................................. 531
21.2 Temporary Halt in the Discovery
of Bioactive Compounds....................... 533
21.3 Future Directions ................................. 533
21.3.1 Genome Mining ........................ 533
21.3.2 Functional Metagenomics .......... 534
21.3.3 Phenotypic Detection
of the Desired Activity................ 534
21.3.4 Induced Gene Expression ........... 535
21.3.5 Sequence-Based Metagenomics . 536
21.4 The Hurdles of Drug Discovery .............. 536
21.5 Marine Pharmaceuticals
Under Clinical Trials ............................. 536
References................................................... 538
In the present chapter, an attempt has been made
to gather detailed information on the present status of coral-derived bioactive compounds and on
the reasons for momentary halt in biodiscovery
of marine natural products, and to outline future
prospects of research on marine/coral associated
bioactive compounds.
21.1 Overview
Marine organisms contain many potential novel bioactive compounds because of the unique environmental
conditions (high ionic strengths, low level of light, cold
or warm temperatures, and pressure) prevailing in their
habitats. Several groups of marine organisms, including soft-bodied sessile invertebrates, such as tunicates,
soft corals, and certain sponges, appear defenceless yet
they produce bioactive compounds to protect themselves from predators. These organisms are rich in
nutritionally important substances and use an arsenal
of chemical defences and chemical repellents to protect
themselves when competing for space. The incidence of
predation is low because of the production of toxic compounds and the possession of some form of calcareous
sclerites. The abundance and diversity of natural products having potential biological activities have provided
scientists with the opportunity to discover new drugs.
In the recent past, bioprospecting of new marine natural products (NMNP) has resulted in the discovery of
several thousand novel molecules. The rich biodiversity