Pfizer Handbook of Microbial Metabolites 312 



Homoserine also is a precursor of threonine in neurospora 

 mutants, with ATP and pyridoxal phosphate required. Threo- 

 nine is synthesized by most microorganisms although it is an 

 essential in mammalian diets. 



The fact that lysine-requiring neurospora mutants use a-ami- 

 noadipic acid makes probable a biosynthetic scheme in which 

 the terminal carboxyl group is reduced and aminated as in the 

 biosynthesis of ornithine from glutamic acid. Some molds even 

 are able to use a-ketoadipic acid, which strengthens the argu- 

 ment. Labeling studies indicate formation of the a-ketoadipic 

 acid by condensation of acetate with either a-ketoglutarate or 

 with the "active succinate" from the citric acid cycle, the acetate 

 carboxyl furnishing the carboxyl group of lysine. Proposed 

 lysine biosynthesis in molds: 



HOOC— CHo— CH2— CO— CoA(COOH) HOOC— CH2— CH2— CH2— C— COOH 

 Active Succinate — > a-Ketoadipic Acid 



CH3-CO-C0A aminationj 



Acetate 



HOOC— CH2—CH2—CH2—CH— COOH 



I 



NH2 

 OCH— CH2— CH2— CH2— CH— COOH < a-Aminoadipic Acid 



NH2 



H2N— CH2— CH2— CH2— CH2— CH— COOH 



NH2 



a-Aminoadipic Acid 

 «-Semialdehyde 



amination 



Lysine 



a-Aminoadipic acid is produced by Penicillium chrysogenum as 

 a component of a tripeptide isolated from the mycelium. It also 

 occurs as a moiety of the antibiotic synnematin-B (cephalo- 

 sporin N) produced by the mold Cephalosporium salmosynne- 

 matum, and it has been isolated from Aspergillus oryzae. 



a,€-Diaminopimelic acid is a precursor of lysine in E. coli and 

 in many other bacteria. L,L-Diaminopimelic acid is formed in 

 E. coli by condensation of pyruvic acid with aspartic acid. 

 Later a specific racemase converts it to the meso-form. A com- 

 plete mechanism for lysine biosynthesis in bacteria has been 

 proposed : 



