5-アミノレブリン酸デヒドラターゼ阻害物質の探索

概要

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More potent inhibitors of 5-aminolevulinic acid dehydratase (ALAD) were screened for use in the microbial production of 5-aminolevulinic acid (ALA) with Rhodobacter sphaeroides and Propionibacterium freudenreichii. Among eight ALA analogues tested, 3-oxoadipic acid (K_i=38μM) and 4-ketopimelic acid (K_i=26μM) exhibited stronger competitive inhibition than levulinic acid (LA, K_i=320μM) for ALAD from P.freudenreichii, but only a small amount of extracellular ALA (16μM) was formed even in the presence of these inhibitors in the medium. On the other hand, for ALAD from R. sphaeroides, 2-oxoadipic acid (K_i=770μM) showed the same inhibitory effect as LA (K_i=480μM), while 3-oxoadipic acid (K_i=210μM) was a slightly stronger inhibitor than LA. When 3-oxoadipic acid was added to the medium at 15mM, extracellular production of ALA increased to 2.5mM, which was about two times greater than the amount obtained when the conventional inhibitor, LA, was used under the same conditions.
社団法人日本生物工学会の論文
1995-01-25