Part E | 27.3
666 Part E Marine Microbiology and Biotechnology
detection of the functions of these genes, and perhaps more efficient biochemical and chemical methods
as well as genomic approaches will allow the discovery of large numbers of novel compounds coded by
these genes. The new mass spectrometry (MS)-guided
genome-mining method that connects the chemotypes
of peptide natural products to their biosynthetic gene
clusters by iteratively matching de novo tandem MS
(MS
n ) data to genomics-derived structures is an example of current effective approaches [27.51].
In a recent review, Lane and Moore [27.52] highlighted the advances made over the last decade (2000–
2010) to improve understanding of the genetic basis of
marine prokaryotic natural product biosynthesis. Initial
studies focussing on identification and sequencing of individual gene clusters provided valuable insights, with
examples including enterocins [27.53, 54] and wailupemycins [27.55]. However, in-depth understanding on the
total quantity and diversity of biosynthetic pathways has
not been achieved as exemplified in these early studies.
The true genetic capabilities of marine microorganisms
have only been revealed when genome sequencing has
become an effective tool to explore the biosynthetic potential of marine microorganisms [27.52].
The first released genome sequences for marine microbes revealed that some of these organisms harbor
genes for biosynthesis of far more natural products than
previously recognized through cultivation-based studies. These orphan pathways, biosynthetic pathways for
which corresponding natural products are unknown,
bring an intriguing possibility that these pathways
might be accessed for discovery of structurally unique,
biomedically useful compounds [27.52].
Bioinformatics studies on the genome sequence of
the first seawater-requiring marine actinomycete, S.
tropica, revealed that this marine bacterial species owns
a large proportion of genes (about 9:9%) responsible for
natural product biosynthesis, while the corresponding
numbers in S. coelicolor and S. avermitilis are 4:5 and
6%, respectively [27.56, 57].
The genome of S. tropica contains an amazingly
large size of genes (516 kb) dedicated to polyketide synthase (PKS) and/or nonribosomal peptide synthetase (NRPS) biosynthesis, which are megasynthases
that are responsible for many active natural product biosynthesis [27.57]. Genome sequence of the
abyssomicin- and proximicin-producing marine actinomycetes V. maris AB-18-032 has also been completed [27.58]. Genome mining studies can reveal
gene clusters for all known molecules from an organism, as well as biosynthetic gene clusters for
natural products yet to be identified. Only through
these studies will the total potential of an organism
as a novel chemistry supplier be identified [27.52].
Discovery of salinosporamide K from S. pacifica by
genome mining has provided insight into pathway
evolution [27.59].
Recent advances in encoding precursor peptides
or biosynthetic proteins, in silico mining of genomes
combined with molecular biology approaches has also
guided the discovery of a large number of new ribosomally derived natural products. Effective strategies
were then designed for the identification of these ribosomally synthesized and post-translationally modified peptides (RiPPs) and the elucidation of their
structures [27.60].
27.3 Ecological and Physiological Perspectives
27.3.1 Metagenomic Approaches
Marine microbial communities have been investigated using cultivation-independent genomic approaches [27.61, 62]. Large scale sequencing of environmental genomes has brought higher resolution
insights into microbial diversity [27.61]. These studies
are thus currently providing a more comprehensive description of the organisms and processes which define
microbial community structure, function, and dynamics
in the sea [27.52].
A more comprehensive view of uncultivated microbial species, gene, and biochemical pathway distributions, and naturally occurring genomic variability is
also becoming clearer as well as fundamental principles that drive microbial ecological and evolutionary
processes are being defined [27.52, 63, 64], with an ultimate goal of sustained development of marine biotechnology [27.63].
27.3.2 Exploring Marine Physiological
Adaptations of Actinomycetes
for Selective Recovery
Penn and Jensen [27.65] recently studied marine adaptations of Salinispora species using comparative ge-
666 Part E Marine Microbiology and Biotechnology
detection of the functions of these genes, and perhaps more efficient biochemical and chemical methods
as well as genomic approaches will allow the discovery of large numbers of novel compounds coded by
these genes. The new mass spectrometry (MS)-guided
genome-mining method that connects the chemotypes
of peptide natural products to their biosynthetic gene
clusters by iteratively matching de novo tandem MS
(MS
n ) data to genomics-derived structures is an example of current effective approaches [27.51].
In a recent review, Lane and Moore [27.52] highlighted the advances made over the last decade (2000–
2010) to improve understanding of the genetic basis of
marine prokaryotic natural product biosynthesis. Initial
studies focussing on identification and sequencing of individual gene clusters provided valuable insights, with
examples including enterocins [27.53, 54] and wailupemycins [27.55]. However, in-depth understanding on the
total quantity and diversity of biosynthetic pathways has
not been achieved as exemplified in these early studies.
The true genetic capabilities of marine microorganisms
have only been revealed when genome sequencing has
become an effective tool to explore the biosynthetic potential of marine microorganisms [27.52].
The first released genome sequences for marine microbes revealed that some of these organisms harbor
genes for biosynthesis of far more natural products than
previously recognized through cultivation-based studies. These orphan pathways, biosynthetic pathways for
which corresponding natural products are unknown,
bring an intriguing possibility that these pathways
might be accessed for discovery of structurally unique,
biomedically useful compounds [27.52].
Bioinformatics studies on the genome sequence of
the first seawater-requiring marine actinomycete, S.
tropica, revealed that this marine bacterial species owns
a large proportion of genes (about 9:9%) responsible for
natural product biosynthesis, while the corresponding
numbers in S. coelicolor and S. avermitilis are 4:5 and
6%, respectively [27.56, 57].
The genome of S. tropica contains an amazingly
large size of genes (516 kb) dedicated to polyketide synthase (PKS) and/or nonribosomal peptide synthetase (NRPS) biosynthesis, which are megasynthases
that are responsible for many active natural product biosynthesis [27.57]. Genome sequence of the
abyssomicin- and proximicin-producing marine actinomycetes V. maris AB-18-032 has also been completed [27.58]. Genome mining studies can reveal
gene clusters for all known molecules from an organism, as well as biosynthetic gene clusters for
natural products yet to be identified. Only through
these studies will the total potential of an organism
as a novel chemistry supplier be identified [27.52].
Discovery of salinosporamide K from S. pacifica by
genome mining has provided insight into pathway
evolution [27.59].
Recent advances in encoding precursor peptides
or biosynthetic proteins, in silico mining of genomes
combined with molecular biology approaches has also
guided the discovery of a large number of new ribosomally derived natural products. Effective strategies
were then designed for the identification of these ribosomally synthesized and post-translationally modified peptides (RiPPs) and the elucidation of their
structures [27.60].
27.3 Ecological and Physiological Perspectives
27.3.1 Metagenomic Approaches
Marine microbial communities have been investigated using cultivation-independent genomic approaches [27.61, 62]. Large scale sequencing of environmental genomes has brought higher resolution
insights into microbial diversity [27.61]. These studies
are thus currently providing a more comprehensive description of the organisms and processes which define
microbial community structure, function, and dynamics
in the sea [27.52].
A more comprehensive view of uncultivated microbial species, gene, and biochemical pathway distributions, and naturally occurring genomic variability is
also becoming clearer as well as fundamental principles that drive microbial ecological and evolutionary
processes are being defined [27.52, 63, 64], with an ultimate goal of sustained development of marine biotechnology [27.63].
27.3.2 Exploring Marine Physiological
Adaptations of Actinomycetes
for Selective Recovery
Penn and Jensen [27.65] recently studied marine adaptations of Salinispora species using comparative ge-