FEDERAL SECURITY AGENCY

PUBLIC HEALTH SERVICE
WASHINGTON 25, D.C.

 

IN REPLYING, ADDRESS THE
PUBLIC HEALTH SERVICE

REFER TO:

Tuberculosis Research Laboratory,
411 East 69th St., New York 21, N. ¥.

November 21, 1951.

Dr. Joshua Lederberg,
Department of Genetics,

The University of Wisconsin,
College of Agriculture,
Madison 6, Wisconsin.

Dear Joshua:

I thought you might like to know about the further follow-up
on some of your mutants, though I don't suppose the details of their
metabolic behavior are very important for your purposes.

W-1427 is a quadruple aromatic auxotroph blocked at the
earliest known site: Ait responds well to shikimic acid or its precursor,
5-dehydroshikimic peda, and Poorly to the next precursor, which we call

Compound We Lio pee’ elutrciig g eg ine

”

SW-38 accumulates a large amount of Compound Zl and small
amounts of shikimic and 22, while W1104, W-1426 and W-1150 accumulate
Z2 and shikimiec, without any Zl.

Z1 and 22 are biologically inactive derivatives of shikimic
acid that yield shikimic acid on autoclaving with acid. 2Z1 seems to
arise at a later step since our several dozen mutants fal]. into the
same groups as yours, namely, accumulators cf Zl plus a trace of 22,
or else of Z2 without Zl.

One excepticnal property of your strains is that W-1426 is an
almost,22 accumulator with very little shikimic, and is uneffected by
the presence or absence of citrate in the medium. This is the behavior
of one of our Aerobacter mutants, whereas our &. coli strains of this
group tend to accumulate a much higher ratio of fw shikinigg.and the ratio
is increased by the presence of citrate. J don't know what all this means
metabolically, but it suggested that W-1426 might be an Aerobacter rather
than a coli, On testing for this possibility, we find it to be an inter-
mediate; in contrast to Aerobacter it does not utilize citrate as a wWiole
carbon source, but in contrast to our W coli its response to glucose is
accelereted by citrate.
Dr. J. Lederberg November 21, 1951.

PF=21 turns out to be no longer an unknown, since it responds
well to B,, or methionine. We found it to be quite unstable and mixed,
so if a pure culture derived from it would be useful to you I would be
glad to send it back, The identification of this mutant proved difficult
since it is inhibited by components of the usual mixtures that we are
at present tracking down. I find this of more than casual interest
since the existence of a By 2/methicnine requirement in coli and By >/
desoxyribosides in lactobacilli has presented something of a mystery.
The presence of the By 2/methionine requirement in a Pseudomonad might
be worth a brief note somewhere. Since this is your mutant, how would
you feel about it? I would rather mention it in the course of some
other paper, but unfortunately have dropped Bio for the time being.
Incidentally, you might be as amazed as I was to iearn that at Merck
they run 2,000 assays a day with our B)>/methionine strain. Just tell
that to your dishwasher}

PF-11, which requires a pyrimidine plus citrulline, ig inter-
esting in utilizing orotic acid as a pyrimidine; wg our corresponding
coli mutant does not. I got PF-11 and PF-21 confused in my letter of
September 28th and hope you will make the correction. FF=21 is leucine
plus B,/methionine.

I wonder whether vou could give me an answer to the question
raised in my latter of October 10th as to whether the methionine plus
lysine requirement of W-1C69 arose from a single mutation. I would like
to mention this fact in discussing POB function at an ACS symposium on
B vitamins in Texas next month.

I hope the washed agar proved satisfactory; if you want a little
more we would be glad to send it, and if you want a regular supply the
recipe is easy to follow.

I thought you might be interested in the enclosed manuscript,
which is being submitted as an editorial in Public Health Reports. It
represents an effort to disseminate Truth among the Masses.

Have a nice Thanksgiving.

Sincerely yours,

<

Deve’.
¢
Bernard D. Davis

BDD/h1