Bioactive Agents from Natural Sources: Trends in Discovery and Application - Advances in Biochemical Engineering Biotechnology - page 104

was discovered by chance from the culture broth of Penicillium notatum as a
bioactive principle inhibiting growth of gram-positive bacteria. In contrast to
plants microorganisms were not known to biosynthesize secondary metabolites
useful in medicinal application until the discovery of the penicillins. In the
following decades microorganisms attracted considerable attention as a com-
pletely new source for pharmaceuticals.Microbial metabolites proved available
at quantities of up to hundreds of kilograms by fermentation technology.From
the screening ofa huge number ofmicrobial extracts an unexpected diversity of
natural compounds performing a broad variety of biological activities became
evident.
Microorganisms turned out to be an unlimited source for both, potential
drugs, and agrochemicals [15-21]. Manufacturing can be performed without
interfering with bioprospecting issues that today considerably hamper industrial
drug development from phytogenic or animal sources.Clinical studies on drug
approval require kilogram amounts of the pure active compounds. Chemical
synthesis cannot solve the problem in the cases of complex structures,as it was
shown by the well known examples of the phytogenic drugs morphine and co-
deine from Papaver somniferum ,quinine from Cinchona species,atropine from
Atropa belladonna , reserpine from Rauwolfia species, vincristine from Catha-
ranthus roseus , or the cardiac glycosides from Digitalis purpurea .However,in
various cases valuable precursors from plants can be made accessible at mode-
rate prices thus contributing to improved manufacturing processes,supplemen-
ted by chemical synthesis,and biocatalysis or biotransformation,respectively.
Precursors are sometimes of considerable advantage because they also give
access to artificial analogs or derivatives which may exhibit a superior spectrum
of properties referring to the demands for a successful drug development and
application. For instance, the manufacture of oral contraceptives and other
steroid hormones based on starting materials of plant origin such as diosgenin
from Dioscorea species and hecogenin from Agave sisalana .
Recently, despite all obstacles hampering large scale production of phyto-
genic drugs,plant metabolites succeeded again in reaching the pharmaceutical
market: The urgent demand for improved chemotherapeutics in anticancer
treatment forced the approval of Taxol (Bristol-Myers Squibb), its analog
Taxotère (Rhône-Poulenc Rorer),topotecan,and irinotecan (Sect.2.5).

2.1
Antibiotics

Since the introduction of the first cephalosporin antibiotic in 1962,every year
several new -lactam antibiotics of the cephalosporin-type have reached the

market.Continual improvement in the activity spectrum is necessary to over-
come resistance phenomena caused by the widespread application of anti-
biotics.Referring to the “hit”-list ofthe commercially most successful therapeu-
tics,three

b

-lactam antibiotics range among the top twenty.These are cefaclor
by E.Lilly,ceftriaxone by Roche,and clavulanic acid as a most efficient

b

-lacta-
mase inhibitor marketed by Smith Kline-Beecham in combination with the
semi-synthetic penicillin derivative amoxicillin under the trade name of Aug-

b