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NATIONAL INSTITUTE FOR, MEDICAL RESEARCH
THE RIDGEWAY - MILL HILL - LONDON, N-W.7.

Cables: NATINMED Mik, LONDON, _,
L. n sae
aX moe 31 May 1956

) MEDICAL RESEARCH COUNCIL

Dear Dr Lederberg, OR

Thank you for your letter of May 27.:. I-am sending off
separately some ampoules of penicillinase which would probably last you
for a very long time, and would save you the necessity of growing up a
culture and preparing some yourself. If you also want subcultures of
strains 5 and 58, I would be very pleased to send you these as well.
Berhaps you could let me know about this.

We are doing a little work at the moment ourselves on
fixation of radiopenicillin by the different strains including, of course,
strain 5 and we would not like to overlap with any work Professor Johnson
is doing along these lines. I think, however, this is rather unlikely as
we are not concerned with the action of penicillin as an antibiotic. If,
therefore, Johnson would to work with strain 5, I should be only too
delighted to send him a ie I will wait to hear from him or you on
this matter.

The *normal function" ¢& penciilinase is, of course, a
matter we /aye worried a lot about. From 9 onary point of view,
I do not think it is surprising to find the of this enzyme in
strains of B.cereus, which is a soil and water organism and, therefore,
may well have encountered penicillins of various kinds in the soil during
its evolutionary*history: =°This seems espedtally more likely now that the
range of different:types*of penicillins is known to be wider than was at
first: expected. =I think the occurrence of penicillin, or at least,
substances closely related to penicillin may be much apmmoner than most
People realise.

We have done a bit of work on substrate and inducer
specificity for penicillinase, and although I gave.a paper.at. Brussels last
year, the work has not yet been written up. I will send you a copy as soon
as it has. The side chain dees not appear to affect the function of
pencillin either as a substrate or an inducer ve ¥ greatly, but - with one
exception - any "tampering" with & pencillin nucieus compietely destroys its

‘ty to fimotion either as substrate or inducer... The exception is a
most’ interesting substance - Cephalosporin ¢ - produced ‘by a species of
Cephalosporium and. discoyered. by Abraham and Newton, ..It is chemically.
very closely related to aminvadipic pentoillin (= cephalosporin N) $a, does
not yield penici as a bréakdown product. This Cephalosporin C is the
most powerful inducer of peniciljinase in Bocereus we have yet encountered,
but is not apparently ‘attacked by the enzyme at all... It appears to compete
with benzylpenicillin to react with the "induction centre" and I suspect that

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it competes with benzylpenicillin also for combination with the specific
penicillin receptor in the cell,

I hear you may be visiting Australia next year and I hope there
May be a chance that you will visit this country on your way there or on
your way back. It would be a great pleasure to have the chance of
meeting you and I very much hope such an opportunity will arise.

Yours sincerely, -
Maria, Pritave
Me R. Pollock.

Dr. J. Lederberg,

Department of Genetics,

University of Wisconsin,
Madison, 6, Wisconsin.