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Abstract: Natural Products are very valuable
pharmaceutical leads due to their potency against often
difficult targets, but they can suffer from issues such
as poor Pharmacokinetics, and their intractability to
synthetic chemistry has hindered their use. The rapid
advancement in molecular biology, such as rapid gene
sequencing, has facilitated the wider application of
bioengineering as a viable approach for Natural Product
lead optimisation to a development candidate. Due to
their intrinsic structural diversity and
assembly-line-like biosynthesis, polyketides are
particularly appropriate for this approach, but other
Natural Products, such as peptides, are also suitable.
Introduction
For thousands of years, natural products have played an
important role throughout the world in treating and
preventing human diseases. Historically, the majority of
new drugs have been generated from natural products
(secondary metabolites) and from compounds derived from
natural products. During the past 15 years,
Pharmaceutical industry research into natural products
has declined, in part because of an emphasis on
high-throughput screening of synthetic libraries.
Currently there is substantial decline in new drug
approvals and impending loss of patent protection for
important medicines. However, untapped biological
resources, “smart screening” methods, robotic separation
with structural analysis, metabolic engineering, and
synthetic biology offer exciting technologies for new
natural product drug discovery. Advances in rapid
genetic sequencing, coupled with manipulation of
biosynthetic pathways, may provide a vast resource for
the future discovery of pharmaceutical agents.
There is a current trend of discovery and applications
of bioactive agents from natural sources. According to
Grabley and Thiericke (Grabley and Thiericke, 1999),
natural products account for 30% of international drug
sales. Although recombinant proteins and peptides have
been accounting for an increasing amount of sales, the
superiority of low-molecular mass compounds in human
disease therapy remains undisputed, mainly due to more
favorable compliance and bioavailability. To meet the
demand for the thousands of test samples that must be
submitted for highthroughput screening (HTS), it is
essential to successfully compete with the rigors of
combinatorial chemistry by developing new strategies in
natural product chemistry. HTS enables the testing of a
large number of samples. Therefore, new concepts that
can generate large collection of compounds that possess
improved structural diversity are desirable. In the
historical context and as a brief background, the
discovery of antibiotics clearly ushered in a new
approach for treating patients. It was entirely
fortuitous—a byproduct of serendipity, a circumstance
that scientists yearn for but from which they often do
not benefit. In many respects, a template for
complementary and alternative medicine (CAM) was being
formed. Unlike this valuable discovery, and the
currently emerging paradigm, the world of natural
products has been awaiting more beneficial exploitation
for several millennia. After all, what were people using
as remedies.
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