!!Zdenko Vaněk - Biography (1987)

!Germination

I was born in the Stará Paka Mountains in Eastern Bohemia in a typical mountain log house
belonging to my mother's parents. There were
already five huts in the mountains, and the nearest village was two kms away, down a stony
road passable only with a horse and cart. All around was marvelous, virginal nature. I always
had a feeling that an integral part of nature were my grandmother and grandfather earning their living from the woods and what the poor fields yielded.
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I lived with my parents in Slovakia. My father was a metal worker by profession. He soon,
however, started a career in the civil service.
The peaceful atmosphere of our family life was
disturbed by the death of my mother. I was then
twelve years old. My father remarried and the
second marriage was also a very harmonious one. I
always rememher my father as a very wise and
foresighted man who inconspicuously guided my
development along the right lines. I was given a
tennis racket when I was ten and a really good
microscope two years later.
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Unfortunately, in 1939, the sky above Europe
began to cloud over and Czechoslovakia was broken
and occupied by the German Army. I finished secondary
school but, in 1943, the universities were
closed. For two years I worked as an auxiliary
worker in the aircraft industry (total eingesetzt).
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!Unripe Raspberries

After the war I began to study at Charles
University in Prague, first in the Faculty of
Pharmacy from which I graduated in 1949, and then
I continued on in the Faculty of Natural Sciences,
specializing in microbiology and chemistry.
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At the Institute of Microbiology of Charles
University, I investigated autolysis of mycobacteria.
Before long, I realized that I could
remain on this problem till the end of the
millennium, thus I voluntarily joined the group
isolating actinomycetes and testing them for their
antibacterial activity. At that time, we had
practically no experience with actinomycetes and
less so with their identification. We obtained
well-defined soil samples from various agricultural
research centers from Bohemia and Moravia
from which the actinomycetes were isolated. Soon
we had a collection of several thousand strains
with different pigmentation of substrate and
aerial mycelium, strains of different smells and
actimicrobial activity. Day after day, it became
obvious that we would not solve the problems of
the isolation and chemical characterization of
potentially interesting compounds by enthusiasm
alone.
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These were really pioneer times; the continuity
was missing; a nurober of professors had
not returned from concentration camps; some of
them had died; modern textbooks were missing, everything was being created and improvised. When
studying for the last year at the University, I
was already on the staff of the Central Biological
Institute of the czechoslovakia Academy of
Seiences, under the directorship of Academician
Ivan Malek. At that time, the Czechoslovak
Pharmaceutical Industry had started to function
and that is why my Ph. D. thesis problem was to
solve "Some problems of the biosynthesis of
Chlortetracycline in ''Streptomyces aureofaciens''"
(1956). I did not anticipate then that I would
remain faithful to problems of the biosynthesis of
biologically active compounds from actinomycetes
for my whole active scientific life. My thesis
for the Doctorate in Science was entitled
"Speculations on the biogenesis of oligoketide
type compounds" and it included largely results
of experimental work with ''S. aureofaciens'', ''S.
erythreus'' and ''S. noursei'' and generalizations which
could be derived from it.
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!A Bit of Luck

In 1958, at the Biochemical congress in
Vienna, I delivered papers on the biosynthesis of
erythromycin. This was the first experimental
proof, using radioactive precursors, of the origin
of erythronolide from propionate. The propionate
rule was not universally accepted at that time.
Following contacts with Professor E. P. Abraham
and A. J. Birch, I had the opportunity of spending
several months at the Institute of Organic
Chemistry in Manchester in 1959 and, some years
later (1964), at the Department of Biochemistry,
Western Reserve University, Cleveland, with J. w.
Corcoran. From these stays, an everlasting scientific
friendship evolved as expressed, by among
other things, the fact that other research workers
from the Department of Biogenesis of Natural
Products went also for long-termed stays to the Institutes mentioned above. Those stays played a
significant role in the establishrnent of an
independent physico-chemical laboratory with
outstanding modern equiprnent (NMR, MS) for resolution
of chernical structures of natural cornpounds
within the Departrnent of Biogenesis.
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I also had the chance to visit the USSR
several times and to institute good working
relationships with the Institute of New
Antibiotics in Moscow (Professor G. F. Gause),
with the Moscow University Laboratory of Professor
N. A. Krasilnikov, and the All Union Scientific
Research Institute Puschino (Professor G. K.
Skryabin) above all.
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!Growth Phase

In the course of years, the Departrnent of
Biogenesis of Natural Products of the Institute of
Microbiology in Prague had stabilized to include
40 professionals. It is a very heterogeneaus team
composed of microbiologists, geneticists, biochemists,
organic and physical chernists, and even
mathernaticians.
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I soon realized that, in the basic research
of natural products, we could go forward much
faster if a better understanding and closer
cooperation between representatives of particular
science branches ( e. g., genetics and chernistry)
could be evoked. That is why we organized in
1969, at the occasion of the Congress of
Antibiotics, a panel discussion entitled "Basic
research and practical aspects of antibiotics",
which gave rise to a book called "Biogenesis of
Antibiotic Substances" (Vanek and Hostalek, eds.)
where, e.g ., s. I. Alikhanyan, G. Serrnonti,
J. A. Roper, J. F. Staffer, H. A. Lechevalier, and C. Spalla, wrote the part on biology; and E. P. Abraham, J. 0. Bu'Lock, c. H. Hassal, J. R. D. McCormick, V. D. Celmer, R. Bentley, 0. Gottlieb, S. Gatenbeck, R. Donovick and others were involved in the biochemical and chemical part.
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Further work was stimulated by the invitation
to give a lecture at the Fifth Interscience
Conference on Antimicrobial Agents and Chemotherapy
and the IVth International congress of
Chemotherapy in Washington in 1965. I presented
our results dealing with antibiotics with glutarimide
ring. The prevailing part of the work was ·
done on cycloheximide produced by ''S. noursei''
and a minor part on streptimidone produced by ''S. rimosus'' ssp. ''paromomycinus''.
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We proved that these compounds belong to a
great family of oligoketide type compounds and
that methyl groups of dimethylcyclohexanone nucleus
originate by transmethylation reactions. The
strain ''S. noursei'' we were working with also produced
nystatin, a compound of the polyene type
with a macrolide ring. When trying to prepare
high-producing mutants of either nystatin or
cycloheximide alone, we found that ''S. noursei'' prevent overproduction of toxic cycloheximide 'by
elaborating an actiphenol compound biologically
completely inactive, biogenetically conformable to
cycloheximide, however, the dimethylcyclohexanone
nucleus is fully aromatized. We presume that this
reaction should be subjoined to already known
detoxification mechanisms like acetylation,
phosphorylation, adenylation in aminoglycoside
producing actinomycetes.
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I was asked by Professor R. Hütter in 1977 to
deliver, at the 5th FEMS Symposium on Antibiotics
and Other Secondary Metabolites-Biosynthesis and
Production in Basel, the results we obtained
during the twenty years of our study of the biosynthesis of tetracyclines in Streptornyces
aureofaciens. These works are well fixed in the
subconsciousness of people engaged in the biosynthesis
of antibiotics. The problern is still
being developed and our Jsllowledge is still being
extended and cornpleted (Hostalek and Vanek, 1986).

!Harvest of Raspberries

Over the course of years, I became convinced
that the problem of industrial overproduction of
microbial metabolites has its own scientific base
which markedly differs frorn the problern of the
production of microbial secondary metabolites in
soil under natural conditions. We, therefore, had
organized the Firs:t International Symposium of
Genetics of Industrial Microorganisrns (GIM) in
Prague in 1970, which gave rise to books: Volume
I, Bacteriaj Volurne II, Actinornycetes and Fungi
(Vanek, Hostilek and Cudlin, eds.). The necessity
of such meetings is best dernonstrated by the fact
that Symposia GIM are being held regularly every
four years. The next one - the sixth - will be
held in France, in 1990, and, the one after in
1994, in Canada.
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At the meeting in Sheffield in 1974 (GIM II),
an International Steering Committee, under the
chairmanship of Professor Sermonti, was established
with a majority of the scientists dealing
with actinomycetes. The prevalence of people from
this branch of genetics is keeping to our days.
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We have postulated in our lecture in Basel,
and even earlier (Pure and Applied Chernistry -
Vanek et al., 1973), that the so-called preparatory
phase (lag phase) is extremely significant
for the production of antibiotic cornpound, that is
the interaction of germinating spores and young cells of actinomycetes with the outside environment
before the phase of reproductive growth.
According to our idea, a new choice of metabolic
programs occurs in this preparatory phase. In
cither words, even in this early phase of the
development of actinomycetes, it is already
programmed and determined which metaballte type
will unreel in the later hours of fermentation,
antibiotics included. This idea was not generally
accepted. What is not yet, could be later. New
data, e.g., on variability and instability of
actinomycete variants, recalled by means of spontaneaus
deletion of chromosome and very high copy
nurober, amplified DNA sequences in the place of
deletion, contribute to this idea.
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The production of secondary metabolites,
under, natural conditions in wild, unimproved
strains of actinomycetes and overproduction of
excessive metabolites by mutant strains, interest
me greatly at present. I am convinced that the
study of the ecology of actinomycetes will give us
a clue to understanding the function of
biologically active compounds. The knowledge of
this function will help in the screening of new
compounds, and in the preparation of high
producing mutant strains.
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For reasons mentioned above, initiated
a symposium in Hradec Králové, dedicated
exclusively to this problern (Overproduction of Microbial Products, Academic Press, 1982, Krumphanzl, Sikyta, Vanek eds. The International Symposium dealing with these relevant
questions will be held in Ceske Budejovice
next year (1988). In preparation to the Symposium
in Hradec Králové, we prepared a book entitled
"Physiology and Pathophysiology of the Production
of Excessive Metabolites" (Vanek et al., 1981).
Several times, I tried to develop the idea of
pathophysiology of overproduction, e.g., Physiology and Pathophysiology of Secondary
Metabolite Production (Vanek and Blumauerova -
in Overproduction of Metabolites strain Improvement
and Process Control Strategies, Vanek,
- Hostalek, Butterworths, eds. , 1986).
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!Have I Done My Best?

If I had to evaluate my nearly forty years
(fortunately not yet finished) werk on the problern
of production of biologically active compounds in
actinomycetes, I must confess that with the
experience I now have, I would try to solve a
nurober of problems differently. This idea is
illusory indeed. Semething or other could be
influenced to some extent, few other things roll
by without our interference. Nothing can be
brought back. I began as a biologist, however, I
soon became captivated by the biochemistry and
chemistry of natural compounds. We built up, with
joint forces in the Institute of Microbiology, a
workplace where very complicated problems of
modern biotechnology could be solved. At the same
time, the proper problern of the biology of
actinomycetes lagged a b,it behind. We have not
succeeded to develop in both directions with the
same intensi ty. Let' s hope we succeed in making
up for it.
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During the past forty years, I met many wise
men, enthusiastic over their scientific werk,
who were rewarded with much scientific success.
Perhaps the more successful they were, the more
modest and friendly they were as people. I greatly
esteem the meetings and discussions with those
people.
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I had the opportunity to visit many different
countries, scientific institutes and universities.
I prefer Europe. I love differences. The roots of our culture are the same. However, Italy is
different, where throughout the place thousands of
years of history could be felt. It is not by mere
chance that the Italians have the best built cars
and set the tone in men's fashion, etc. Thousands
of years of genetic material remain there and only
appear phenotypically in another way. I could say
the same, however, about the French, Spaniards,
and Greeks. How different are the English,
Germans, Russians, Dutch, and swedes on the other
hand? How different are the countries where
they are living? In Europe, within a 50-100 km
distance, you can travel in a completely different
countryside, with different atmosphere, and with
different people.
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!The Best to the End

I belong to the group of people who need a
calm family background for work. I married a
microbiologist, Dr. Jirina Suchomelova, Ph.D.,
who worked at the Entomological Institute of the
Czechoslovak Academy of Seiences. However, what
I can't comprehend is how she was able to cope
successfully with both work and family. In addition,
she created enough space and time for me
so that I could devote almost all my time to my
hobby - the metabolism of actinomycetes.