microorganisms: oxidizing mutant found
TRANSCRIPT
Kodak's Schaeffer Goodhue Sara and Serendipity showed the way
that Dr. LeMaistre admits he had never considered before.
If the work being presented in Atlantic City is any example there is not likely to be any widespread hue and cry to do away with national meetings. Symposiums and papers range from coverage of the long ago and far away at a two and a half day discussion of the chemistry involved in archeologi-cal studies—to the here and now at a symposium that will attempt to point out more clearly the importance of basic scientific research to the nation today.
The archeology symposium will deal with how analysis of coins, pottery, and other materials by electronic, nuclear, and chemical means can be used to decipher the mores of ancient societies.
Dr. Donald F. Hornig, Special Assistant for Science and Technology to President Johnson, will be one of five scientists taking part in the second symposium, "The Functions and Future of Basic Research." Dr. Franklin A. Long, vice president for research and advanced studies at Cornell, will preside at the symposium, which is being sponsored by the Society's Committee on Chemistry and Public Affairs.
In the Division of Medicinal Chemistry a Thursday symposium on chemical mediators of information transfer will deal with the latest theories on the biochemistry of taste and smell.
Also in the medicinal division, Dr. Frances E. Knock of Augustana Hospital, Chicago, will report on progress in the development of an oral anticancer agent.
In the Division of Cellulose, Wood, and Fiber Chemistry there will be a report on Hercules' new hydroxypro-pyl cellulose—a chemical modification whose useful properties range from that of serving as a stabilizer in foods to the capability of being injection molded into plastic parts.
In the same division, Dr. Warren D. Kitts of the University of British Columbia, Vancouver, and others, will outline treatments for wood and its by-products through which they can be turned into food for cattle and other ruminants.
The Division of Agricultural and Food Chemistry will host a symposium on the effects of pesticides and their metabolites on biochemical processes.
There will be symposiums on new uses for asphalt (sponsored by the Petroleum Division) and forensic chemistry (sponsored by the Division of Analytical Chemistry), among the remainder of the 2056 scientific papers and 308 technical sessions which make this September's meeting the largest fall session ever put together by American chemists.
MICROORGANISMS:
Oxidizing Mutant Found Mutant strains of a newly discovered organism, Flavobacterium oxydans, oxidize pentaerythritol to tris (hydroxy-methyl) acetic acid in almost quantitative yields. The finding is significant because it provides a simple, direct route to the acetic acid derivative, Eastman Kodak's Dr. Charles T. Goodhue told the 3rd International Fermentation Symposium (cospon-sored by ACS and the International Union of Pure and Applied Chemistry) at Rutgers University. Chemical methods of oxidizing pentaerythritol, on the other hand, give poor yields of the product besides being hazardous and expensive to carry out on a large scale, he notes.
Dr. Goodhue is guarded about his company's interest in tris (hydroxymethyl) acetic acid. Other than saying that it's an intermediate for making "a photographic chemical/' he maintains a discrete silence on the subject.
"Besides seeking a better route to tris (hydroxymethyl) acetic acid, we were interested in studying the biological oxidation of pentaerythritol. Although it doesn't occur in nature, the polyol might appear to a microorganism to be similar to a simple sugar," Dr. Goodhue comments.
Working with Dr. James R. Schaeffer at Eastman Kodak's research laboratories in Rochester, N.Y., Dr. Good
hue made numerous abortive attempts to isolate from soil samples organisms that would metabolize pentaerythritol either as a primary or secondary carbon source. They were on the point of shelving the project when they examined some mud that Dr. Goodhue's nine-year-old daughter, Sara, had collected from a nearby creek. 'This mud yielded the pentaerythritol-feed-ing bacteria that after appropriate manipulation and training obedien reproduced tris (hydroxymethyl) acetic acid."
Flavobacterium oxydans had remained undetected until now. It is gram negative, nonmotile, yellow, and rodlike. The organism normally feeds on pentaerythritol without need for
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THE CHEMICAL WORLD THIS WEEK
any other carbon source. But in so doing, metabolism goes all the way to carbon dioxide and water. However, Dr. Goodhue and Dr. Schaeffer isolated and nurtured mutant strains that oxidize pentaerythritol only when other carbon sources, such as acetic acid, are present. Fortuitously, the mutant lacks the enzyme system that breaks down tris (hydroxymethyl) a-cetic acid.
In a typical experiment, the Eastman Kodak scientists grow the mutants in a sterile solution comprising 20 grams of pentaerythritol, 10 grams of yeast extract, and 2 grams of acetic acid per liter of water. (Before sterilization, the pH of the solution is adjusted to 7.0 with potassium hydroxide.) During fermentation, they maintain the temperature at 30° C. and keep the contents of their flasks constantly agitated. Tris (hydroxymethyl) acetic acid is separated from the fermentation broth by adsorption on an ion exchange resin column and eluted with formic acid. Recrystal-lization of the product recovered after evaporation yields the acetic acid derivative that's "at least 99% pure." elemental and melting point data, together with spectrometric profiles of the trimethylsilyl derivative, match those of the sought-after material.
Dr. Goodhue and Dr. Schaeffer find that stepwise addition of pentaerythritol (up to a 60 gram-per-liter concentration level) and neutralization of the acid as it forms result in almost a quantitative yield of tris (hydroxymethyl) acetic acid within 11 days. Success of the operation is keyed closely to the conditions employed. For example, yield drops if the fermentation rate isn't carefully controlled.
BIRTH CONTROL:
Upjohn Disarms Sperm A new approach to male antifertility drugs may be shaping up. Upjohn has conducted animal tests with two new experimental compounds that render male rats infertile for long periods without destroying ability to mate. The drugs are neither anti-spermatogenic nor spermicidal. In fact, at this time their precise mode of action has not been ascertained by Upjohn scientists.
Details of research carried out on the compounds by scientists at Up-john's Kalamazoo, Mich., laboratories were reported by Dr. R. J. Ericsson in Nashville, Tenn., at the annual meeting of the Society for the Study of Reproduction. The two compounds, U-5897 and U-15,646, are chlorohy-drins. Currently, Upjohn is concen
trating its work on U-5897, chemically 3-chloro-1,2-propanediol.
So far, most work on male antifertility drugs has been with antispermato-genic agents—those that prevent the production of sperm. Ortho Research Foundation, for example, has worked with 2,4-dinitropyrroles and Sterling-Winthrop with some halogenated diamines. Upjohn itself carried out some initial studies with steroids, but these studies are no longer continuing.
A number of problems have impeded work with antispermatogenic agents. One problem, for example, involves appearance: testes decrease in size considerably. There is also risk of genetic abnormalities. And, in at least one case, there is severe reaction if a person drinks alcohol while using the drug.
Upjohn scientists aren't sure how the new compounds work. Studies with rats, guinea pigs, and monkeys show that they do not prevent production of sperm nor do they kill them. Dr. Ericsson says that the Upjohn scientists believe the compounds work on the epididymal vascular system. They may interfere, he says, with the sperm's oxygen supply or allow the accumulation of metabolic wastes which make the sperm ineffective.
Evidence that the compounds exert their effect in some area beyond the testes is the speed with which they take effect. Lowered fertility begins four to five days after treatment starts, a shorter period than it takes for sperm to traverse the epididymis after leaving the testes. Fertility returns, moreover, within a week after treat
ment stops. With antispermatogenic agents, resumption of fertility takes three months or more.
However the compounds work, they do not impair testicular function. Sperm look normal and act normal, except that they are incapable of fertilizing the ova. This was the case even for rats treated for seven weeks with twice the effective minimum dose of U-5897. Fertility of treated animals was tested by weekly or biweekly ma tings.
CAPITAL INVESTMENT:
CPI Spending Slacks Off Early indications are that capital expenditures by the chemical industry in 1969 will show a decline for the third year in a row. The latest quarterly capital investment survey by the National Industrial Conference Board puts unspent chemical industry capital appropriations at their lowest level since the end of 1964. A C&EN spot check of 10 major chemical companies reveals that they plan to spend a total of about 4% less next year than they estimate they will spend this year. And a new report by the Department of Commerce indicates that capital expenditures by U.S. Chemical Affiliates abroad are due to drop 23% next year. The NICB study puts chemical makers' unspent appropriations at mid-1968 at $2.08 billion. This compares with $2.64 billion a year earlier and $2.77 billion at the midpoint of 1966. New appropriations are also down sharply to a seasonally adjusted $504
Plant abuilding Less activity in '69 for third straight year
SEPT. 9, 1968 O&EN 19