Marine Actinomycetes in Biodiscovery 27.5 Future Prospects 671
Part E | 27.5
tive fitness of the bacteria attributed primarily to their
ability to generate reactive oxygen in other organisms
and tissues [27.96]. The competitive environment of
the near shore marine environments including pollution
from human activities and presence of marine macroorganisms might be triggering the production of these
compounds.
Penn et al. [27.97] has recently identified that genomic islands can harbor functional traits that differentiate ecologically distinct populations of environmental
bacteria. Their comparative analysis of the complete
genome sequences of the marine actinobacteria S. tropica and S. arenicola revealed that 75% of the speciesspecific genes were located in 21 genomic islands.
These islands were enriched in genes associated with
secondary metabolite biosynthesis providing evidence
that secondary metabolism linked to functional adaptation. Brominated and chlorinated compounds produced
by the USC-633 might also be as a result of such functional adaptation.
27.5 Future Prospects
Traditional approaches have been successful at identifying many successful therapeutic agents since the
discovery of penicillin. However, growing antibiotic
resistance and need for potent agents to combat
many incurable diseases indicate the urgent need for
new approaches. The application of genome mining,
metabolomics, and proteomic tools has recently been
a leading force in developing novel advances in the drug
discovery area. They will continue to be the driving
forces for discovery and design of potent therapeutic
agents from microbial sources in the years to come.
Through these advances the true biosynthetic potential and metabolic diversity of marine microorganisms
will be revealed [27.98, 99]. Cross-country advances in
bioinformatics tailored for the marine field, consistent
data acquisition and exchange and design of relevant
marine bacterial models is now a recognized priority in
Europe resulting in an EU funded series of workshops
and projects [27.100].
Genome sequences will continue to provide valuable insights for activation of silent gene clusters [27.99]. One of the most successful outcomes
via the use of genomic approaches has so far been
through the studies conducted on Salinispora species.
Examples include the exploration and engineering of
biosynthetic pathways in the marine actinomycetes S.
tropica [27.101] and the discovery and assembly line
biosynthesis of the lymphostin pyrroloquinoline alkaloid family of mammalian target of rapamycin (mTOR)
inhibitors in Salinispora [27.102].
High-throughput genome scanning methods will
also facilitate discovery of metabolic loci-independent
of expression. Genome sequence tags (GSTs) are genes
involved in natural product biosynthesis and they can be
utilized as probes for screening of specific genes within
clonal libraries. Subsequently, any clone that contains
a GST can then be screened for novel natural product
gene clusters such as the identification of more than 450
natural product clusters [27.50, 103]. Genome inspiredtechnologies will also unveil new metabolites which
were overlooked under standard fermentation and detection conditions.
Advances in the chemistry field will continue to
facilitate rapid discovery of bioactive molecules using improved ability to dereplicate, isolate, and elucidate the structure of natural products from reduced
sample quantity [27.3]. Emerging physiology-oriented
engineering strategies based on improved understanding into microbial physiological responses to environmental stresses, will also result in productive
physiological performances of industrial microorganisms [27.104].
Microbial ecotypes [27.105] or geovars [27.106]
can also be specific to a geographical–ecological region, for example more than 200 secondary metabolites
have been isolated from various Streptomyces hygroscopicus strains of different geographical origin. Moreover, strains of the same subspecies may produce different compounds [27.50]. Jensen and Mafnas [27.25]
following their studies using tropical and subtropical
ocean sediments conclude that Salinispora species are
globally distributed and speciation within this genus
is driven by ecological selection not geographical isolation. The reported presences of indicator bacteriophages specific to Salinispora type strains in different
geographical regions by Kurtböke [27.74] also support
their conclusions.
Biogeographical information combined with metagenomics-derived data will give insight into population dynamics of predominantly unculturable microbial
communities. It will also provide information into the
capabilities of microorganisms that allow them to collaborate and compete to survive in a wide range of
environments [27.107]. The application of new molec-
Part E | 27.5
tive fitness of the bacteria attributed primarily to their
ability to generate reactive oxygen in other organisms
and tissues [27.96]. The competitive environment of
the near shore marine environments including pollution
from human activities and presence of marine macroorganisms might be triggering the production of these
compounds.
Penn et al. [27.97] has recently identified that genomic islands can harbor functional traits that differentiate ecologically distinct populations of environmental
bacteria. Their comparative analysis of the complete
genome sequences of the marine actinobacteria S. tropica and S. arenicola revealed that 75% of the speciesspecific genes were located in 21 genomic islands.
These islands were enriched in genes associated with
secondary metabolite biosynthesis providing evidence
that secondary metabolism linked to functional adaptation. Brominated and chlorinated compounds produced
by the USC-633 might also be as a result of such functional adaptation.
27.5 Future Prospects
Traditional approaches have been successful at identifying many successful therapeutic agents since the
discovery of penicillin. However, growing antibiotic
resistance and need for potent agents to combat
many incurable diseases indicate the urgent need for
new approaches. The application of genome mining,
metabolomics, and proteomic tools has recently been
a leading force in developing novel advances in the drug
discovery area. They will continue to be the driving
forces for discovery and design of potent therapeutic
agents from microbial sources in the years to come.
Through these advances the true biosynthetic potential and metabolic diversity of marine microorganisms
will be revealed [27.98, 99]. Cross-country advances in
bioinformatics tailored for the marine field, consistent
data acquisition and exchange and design of relevant
marine bacterial models is now a recognized priority in
Europe resulting in an EU funded series of workshops
and projects [27.100].
Genome sequences will continue to provide valuable insights for activation of silent gene clusters [27.99]. One of the most successful outcomes
via the use of genomic approaches has so far been
through the studies conducted on Salinispora species.
Examples include the exploration and engineering of
biosynthetic pathways in the marine actinomycetes S.
tropica [27.101] and the discovery and assembly line
biosynthesis of the lymphostin pyrroloquinoline alkaloid family of mammalian target of rapamycin (mTOR)
inhibitors in Salinispora [27.102].
High-throughput genome scanning methods will
also facilitate discovery of metabolic loci-independent
of expression. Genome sequence tags (GSTs) are genes
involved in natural product biosynthesis and they can be
utilized as probes for screening of specific genes within
clonal libraries. Subsequently, any clone that contains
a GST can then be screened for novel natural product
gene clusters such as the identification of more than 450
natural product clusters [27.50, 103]. Genome inspiredtechnologies will also unveil new metabolites which
were overlooked under standard fermentation and detection conditions.
Advances in the chemistry field will continue to
facilitate rapid discovery of bioactive molecules using improved ability to dereplicate, isolate, and elucidate the structure of natural products from reduced
sample quantity [27.3]. Emerging physiology-oriented
engineering strategies based on improved understanding into microbial physiological responses to environmental stresses, will also result in productive
physiological performances of industrial microorganisms [27.104].
Microbial ecotypes [27.105] or geovars [27.106]
can also be specific to a geographical–ecological region, for example more than 200 secondary metabolites
have been isolated from various Streptomyces hygroscopicus strains of different geographical origin. Moreover, strains of the same subspecies may produce different compounds [27.50]. Jensen and Mafnas [27.25]
following their studies using tropical and subtropical
ocean sediments conclude that Salinispora species are
globally distributed and speciation within this genus
is driven by ecological selection not geographical isolation. The reported presences of indicator bacteriophages specific to Salinispora type strains in different
geographical regions by Kurtböke [27.74] also support
their conclusions.
Biogeographical information combined with metagenomics-derived data will give insight into population dynamics of predominantly unculturable microbial
communities. It will also provide information into the
capabilities of microorganisms that allow them to collaborate and compete to survive in a wide range of
environments [27.107]. The application of new molec-