Biosynthetic studies on clavulanic acid: its biopathway and stereochemical course

Thesis/Dissertation · Thu Jan 01 00:00:00 EST 1987

OSTI ID:6281234

Mao, S S

A degradative analysis allowed determination of the stereochemistry at C-9 of clavulanic acid produced by Streptomyces clavuigerus. An over-all inversion of configuration from the C/sub 5/-unit precursor ornithine was observed. The diastereomeric (1R,2R)- and (1S,2R)-(1-/sup 3/H)-glycerols were separately synthesized and administered. Complementary results demonstrated an overall retention of configuration paralleling cysteine incorporation in the biosynthesis of penicillin. 3-Hydroxyornithine, a potential precursor to clavulanic acid, was prepared by a 1,3-dipolar addition of a nitrone and vinylglycine. However, 3-hydroxyornithine was not taken up by the organism and this possible intermediate could not be shown to be a specific precursor to clavulanic acid. (2-/sup 3/H)-L-Ornithine displays a preferential incorporation relative to D-ornithine. An epimerization by a one-base mechanism is suggested by the retention of half the tritium activity. ..beta..-Alanine, a potential precursor of the ..beta..-lactam segment was examined and shown not to play a direct role in the biosynthesis. Further, 3-hydroxypropionyl-ornithine, a parallel amide to the tripeptide intermediate in penicillin biosynthesis, was not incorporated into clavulanic acid. The role of 3-hydroxypropionate and glycerol were examined in both starch and triglyceride fermentation media.

• Research Organization: Johns Hopkins Univ., Baltimore, MD (USA)
• OSTI ID: 6281234
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARBOXYLIC ACIDS
BIOSYNTHESIS
ALANINES
BIOLOGICAL PATHWAYS
GLYCEROL
ORNITHINE
PRECURSOR
STEREOCHEMISTRY
STREPTOMYCES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALCOHOLS
AMINO ACIDS
BACTERIA
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MICROORGANISMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
SYNTHESIS
550201* - Biochemistry- Tracer Techniques