Chemistry Reference
In-Depth Information
the market today and are agriculturally beneficial. Biologically active compounds
have only been isolated from a very small percentage of the microbial diversity
found in a given ecosystem or geographic area (2, 3). Through the use of molec-
ular biology and other identification techniques, it is estimated that less than
1% of microbial diversity has been cultured and studied experimentally (approx-
imately 6,000 species of prokaryotes and approximately 70,000 fungal species
have been formally described) (4-7). Therefore, new species of fungi and actino-
mycetes, with metabolic pathways adapted for life in a wide range of terrestrial
and marine environments, are being discovered every day. Microbes living in
unique environments may produce a variety of unusual metabolites, allowing for
the discovery and application of new chemical compounds.
The list of microbial natural products with biological activity is long and
includes compounds that have had a widespread impact on agriculture, human
and veterinary medicine, the food industry, and scientific research. The biolog-
ically active portion of some compounds contains unusual chemical structures
that are crucial therapeutic agents with uses in oncology, immunosuppression,
atherosclerosis, and the treatment of infectious diseases. Several microbial nat-
ural products also have antioxidant properties; can protect against radiation; are
able to boost cellular tolerance to desiccation, salt, and heat stress; and are even
used in microbial chemical intercommunication.
Approximately 22,500 metabolites reported to exhibit biological activity have
been isolated from actinomycetes or fungi, with 45% of such compounds pro-
duced by actinomycetes, 38% by fungi, and 17% by unicellular bacteria (8). To
date, new microbial products are in clinical development, particularly as anti-
cancer agents and anti-infectives.
Similar biological effects are often displayed by different chemical species,
giving rise to the concept of chemical diversity. This chapter focuses on the active
metabolites that have been evaluated for their biological, pharmacological, and/or
chemotaxonomic potential, or for the purpose of exploring chemical diversity.
3.1 ANTIBACTERIALS
Microbially produced secondary metabolites are extremely important to our health
and nutrition. As a group, they have tremendous economic importance. In 2007,
the market for antibiotics was US$66 billion (1) and included approximately 160
antibiotics and derivatives.
3.1.1
β
-Lactams
β
-lactam antibiotics act by inhibiting cell wall synthesis and are the largest and
most often used group of antibiotics in the clinic because of their wide therapeutic
range and low toxicity.
Penicillins (
1
) are the main exponent of the
β
-lactam group. This group of
antibiotics was isolated from the fungus
Penicillium notatum
. Members consist
