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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.