Information Technology Reference
In-Depth Information
unanalysed modular polyketide and peptide gene-clusters and to design primers for cloning
left and right ends of gene-clusters in order to be able to pull out the entire clusters that are
often larger than 100 kb. Computer programmes for modelling recombination between
modular polyketide and peptide gene-clusters have been developed. The first programme
was written in Turbo PASCAL. The programme outputs a file with the module description
of all recombination products. A further programme, written in Java, uses these data to
generate a chemical description of products of each module and to give graphical
representation of linear polyketide chemical structures [39]. After pre-polyketide and pre-
peptide biosynthesis, polyketides and peptides usually undergo cyclisation reactions. It
would be very interesting to add a programme to model cyclisation reactions in order to be
able to predict the final products in fermentation. To do that a number of PKS and NRPS
databases that have been recently developed (Natural Product Gene Database,
http://www.npbiogene. com/; A Database of Modular Polyketide Synthases,
http://www.nii.res.in/pksdb.html; A knowledge based resource for analysis of Non-
ribosomal Peptide Synthetases and Polyketide Synthases, http://www.nii.res.in/nrps-
pks.html) can be used.
Additional biodiversity can be envisaged from recent findings that have shown
natural existence of mixed complexes. For example, PKS-like modules, responsible for the
incorporation of a polyketide moiety within the peptide chains, have been found. One such
example is the biosynthesis of Bleomycin from
S. verticillus
. And indeed, DNA sequencing
of the Bleomycin gene-cluster showed that the 7
th
module in this enzyme is indeed the PKS
module. NRPS-like modules have also been found within PKSs. In such situations, NRPS-
like modules are responsible for the incorporation of an amino acid moiety within the
polyketide chains as occurs in the biosynthesis of the antibiotic Rifamycin from
Amycolatopsis mediterranei
. Consequently, it is very much likely that PKSs and NRPSs
could also be recombined, both
in silico
and in the laboratory [see references in: 22].
To summarise,
Streptomyces
species and related genera undoubtedly have very
significant genetic biodiversity potential. The structural biodiversity of their secondary
metabolites is also very significant. It has been shown that combinatorial biosynthesis in
Streptomyces
can be used to generate novel chemical entities, so there is an obvious need
for further work with Streptomycetes and their secondary metabolites. The bioinformatic
programmes mentioned would be useful tools for predicting novel polyketide, non-
ribosomal peptide and/or mixed structures
in silico
that might then be produced by an
appropriate genetic manipulation in the laboratory.
4. Conclusions
Genomics, proteomics and bioinformatics have brought about fundamental changes, and
one cannot exist without the other. Development of bioinformatics will shift many
experiments from the laboratory to the computers, although it is obvious that predictions
cannot go without experimental confirmations. The race between companies will be won by
those who will be able to mine databases best, and finally it is also about
brainware
, not
only hardware or software. All these factors seem to point towards an unprecedented
concentration of technological means within the pharmaceutical industry as well as
agriculture. According to a survey of Time magazine, data mining and bioinformatics will
be within the 10 hottest jobs of the 21-century [40]. It is obvious that all biologists have to
be educated in this field.
