Hardick, David James (1992) The biosynthesis of nojirimycins. PhD thesis, University of Warwick.

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Abstract

Streptomyces subrutilus ATCC 27467, when grown on a glucosecontaining
soyabean medium, produces both 1-deoxymannonojirimycin
(DMJ) and 1-deoxynojirimycin (DNJ) in its culture medium. When 1- or
2-[2H]-D-glucose is used, the deuterium label appears at C6 in both
alkaloids and the labelling pattern suggests that the first step in the
biosynthesis of both DNJ and DMJ is a glucose to fructose isomerisation.
Studies with 5-[2H]-D-glucose and 6,6-[2H2]-D-glucose indicate that
oxidation of the 6-position of the glucose/ fructose occurs during the
biosynthesis and that mannonojirimycin is the first amino sugar to be
formed. Mannonojirimycin can then undergo dehydration and reduction
to DMJ. Alternatively, epimerisation of mannonojlrlmycin can occur at
C2 to give nojirimycin which is then dehydrated and reduced to DNJ.
Studies with another microorganism, B. subtilis var niger ATCC
9372, indicate that a similar biosynthetic pathway is in operation. DMJ,
however, is not produced by this microorganism and only low levels of
NJ are postulated from enzyme inhibition and deuterium labelling
studies. A minor biosynthetic route is also evident from labelling studies
with 1-[13C]-D-glucose and 1-[13C]-D, L-glyceraldehyde. It is suggested that
the fructose at the beginning of the biosynthesis can split into two C3
trioses which are in equilibrium with each other. These can then recombine
to continue in the usual biosynthetic pathway.
New chemical routes to 542H]-D-glucose and 2-[2H]-D-glucose are
described in Chapter 3 along with a method for introducing deuterium or
tritium into DNJ or NJ. Other isotopically enriched glucoses or
intermediates have also been prepared using literature methodology.
Studies have been undertaken to assess whether S. subrutilus can
utilise glucose analogues in the biosynthetic pathway. To this end, new or
modified routes to these glucose derivatives have been investigated and
some work has focused on the chemical synthesis of DNJ analogues
themselves.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QD Chemistry
Library of Congress Subject Headings (LCSH):	Antibiotics -- Synthesis, Amino sugars -- Synthesis, Streptomyces
Official Date:	October 1992
Dates:	Date Event October 1992 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Hutchinson, D. W. (David Wesley)
Extent:	191 leaves
Language:	eng

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