D+

PROFESSOR H. L. KORNBERG F.R.S.

401 1%

DEPARTMENT OF BIOCHEMISTRY
UNIVERSITY OF LEICESTER

FROM UNIVERSITY ROAD
LEICESTER LE1 7RH
TELEPHONE: 50000

 

( 4 ! 22nd April, 1974

/whether

Deer &. Lederberg ,

Your very kind letter of 18th April gave me great pleasure,
not only because of your friendly interest but because it convinced me
that there are other and better people whose performance in the writing
field does not quite match up to their intentions! I do not regret
at all having pursued your early publications virtuously because, in the
spirit of the three Princes of Serendip, I found many gems on the way.

My interest in the chloroacetate resistance phenomenon stems
primarily from two soutes. As you may remember from the seminar that
I gave in your School (or, more likely, that you will not remember), I
have for long been interested in the regulation and identity of the
reactions that replenish the tricarbox¥lic acid cycle. It was thus of
considerable interest to determine the fate of halogenated acetate and
it is for that reason that we have, for some years, played about with
fluoroacetate. The mutants that are resistant to fluoroacetate that
we have obtained so far fall into two main classes. The first type
lacks acetatekinase; the second phosphotransacetylase. However, the
first class of mutants still grows slowly on acetate whereas the second
does not: I suspect that this latter class also lacks malatesynthase
which is known to be able to use FAcetyl-CoA as a substrate.

My second reason for being interested is that I have now been
engaged for some years in the study of uptake systems for carbohydrates.
Although such uptake systems are clearly defined for hexoses, pentoses,
and sugar acids derived from them, there is only scanty evidence that
molecules smaller than 3-garbon ace¢etme require a "permease". As you
may note from the reprint’enclosed, we have found an uptake system for
pyruvate. We had hoped to see Where fluoroacetate-resistant mutants were
resistant because they refused to admit fluoroacetate into the cell.

Our data so far suggest that this is not so: there seems to be no unique ,
saturable, genefically- specified, "permease" for acetate. However, I

am still continuing to look, in a desultory sort of way, and had hoped
that the use of something other than fluoroacetate might have shed light
on this.

I was most interested to learn from you that the class of
mutants that you studied were deficient in formic hydrogenlyase. So far
as I am aware, this enzyme is not formed to any significant extent during

Dr. Joshua Lederberg,
Stanford University Medical Center contd/
2 2end April, 1974

aerobic growth and thus plays no role in other than anaerobic conditions.
Am I incorrect in this? If this were correct, it would be difficult
to detect the lesion in aerobic conditions.

I am in the process of writing up some of our work (I really

am!) and shall send you a copy of my paper if/when it is ready for
submission.

With many thanks and best regards,

Sincerely yours,

1. bom
—

Dr. Joshua Lederberg,
Department of Genetics,

Stanford University School of Medicine,
STANFORD,

California 94305, U.S.A.