Studies on the Bacterial Formation of a Peptide Antibiotic, Colistin

Part III. On the Biosynthetic Pathway of α, γ-Diaminobutyric Acid and Relationship between Colistin Formation and Amino Acids Metabolism in Bacillus colistinus KOYAMA

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The biosynthetic pathway of α, γ-diaminobutyric acid, 6moles of which are involved in the colistin molecule as a main component, was investigated. On the basis of the isotopic results using aspartic acid-U-¹⁴C as a precursor and also the finding of transaminase activity between α-ketoglutaric acid and α, γ-diaminobutyric acid, though in reverse reaction, α, γ-diaminobutyric acid was proved to be synthesized from aspartic acid via aspartyl-phosphate and aspartic β-semialdehyde. α, γ-Diaminobutyric acid did not inhibit aspartokinase activity of this bacterium, the first enzyme involved in the process of α, γ-diaminobutyric acid synthesis from aspartic acid, while the end product amino acids such as lysine, threonine and methionine showed inhibition for aspartokinase activity.
On the other hand, α, γ-diaminobutyric acid might be rate-limiting factor in colistin formation, because of stimulatory effect of this diamino acid when added to the medium on colistin production. Furthermore, colistin production appeared to be related with the defect of TCA-cycle and further the resultant increase in activities of the key enzymes such as isopropylmalate synthetase, α-acetolactate synthetase and aspartokinase involved in the biosynthetic pathways of valine, leucine and isoleucine, respectively.