Isolation and structure of leukotriene-A sub(4) hydrolase inhibitor: 8(S)-amino-2(R)-methyl-7-oxononanoic acid produced by Streptomyces diastaticus

The novel amino acid 8(S)-amino-2(R)-methyl-7-oxononanoic acid (1) was isolated from the soil-borne microorganism Streptomyces diastaticus during our screening for inhibitors of leukotriene-A sub(4) hydrolase (LTA sub(4)H), a requisite enzyme in the biosynthesis of the potent inflammatory mediator leukotriene-B sub(4) (LTB sub(4)). The structure of 1 was determined by detailed spectroscopic analyses and is related to 7-keto-8-aminopelargonic acid (2), a biosynthetic precursor of biotin. The relative potency of 1 (LTA sub(4)H IC sub(50) = 0.6 mu M) warranted further biological studies.