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Title: Studies on the biosynthesis of 1-deoxynojirimycin
Author: Trew, Sally J.
ISNI:       0000 0001 3536 3504
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 1992
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1-Deoxynojirimycin (DNJ) is a 1-deoxy-glucose analogue and glucosidase inhibitor which has also been found to inhibit replication of Human Immunodeficiency Virus. It is known to be produced by several strains of Streptomyces lavendulae and in the present study, Streptomyces subrutilus 445 has also been identified as a producer of DNJ and the 1- deoxy-mannose analogue, 1-deoxymannojirimycin (DMJ). DNJ can be assayed in fermentation samples by virtue of its inhibition of pig kidney trehalase, after the removal of the interfering inhibitor no j irimycin by a heat and acid treatment. DNJ and nojirimycin inhibit this trehalase with Ki values of 3.43 x 10-6 and 2.6 x IO-5 M respectively. The production of DNJ in defined media is subject to supression by glucose and phosphate. Addition of ammonium sulphate to the cultures also inhibits DNJ production although it is unclear whether this is purely a supressive effect. Glucose and starch are the best carbon sources and proline the best nitrogen source in defined media containing only one major carbon and one major nitrogen source. Glucose is the biosynthetic precursor to both DNJ and DMJ and a pathway is proposed which involves a glucose to fructose isomerisation, an inversion of the sugar backbone, and an epimerisation of nojirimycin B to nojirimycin.
Supervisor: Not available Sponsor: Science and Engineering Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry ; QP Physiology