Anticancer enzyme L-lysine α-oxidase -: Properties and application perspectives

Fungal L-lysine a-oxidase (1.4.3.14) (LO) from Trichoderma harzianum Rifai presents an oxidoreductase with a firmly attached coenzyme--FAD. This stable enzyme catalyzes an oxidative deamination of L-lysine yielding hydrogen peroxide, ammonia, and a-keto acid. LO exhibits antitumor activity toward 5 of 12 tested transplantable tumors. The sensitive tumors were ascitic hepatoma 22 (T/C = 201%, CR = 66%); mammary adenocarcinoma Ca755 (TGI = 96%); melanoma B-16 (TGI = 81%); AKATOL (TGI = 75%); RSHM 5 (TGI = 79%). LO therapeutic activity was observed within a wide range of doses, 35-350 U/kg, by intraperitoneal daily injections for 5 d. Contrary to Escherichia coli L-asparaginase, LO demonstrates its antitumor activity by the low therapeutic doses in vivo within a wide range of optimal doses and through another antitumor spectrum. Fisher lymphadenosis L-5178y highly sensitive toward L-asparaginase appeared to be LO resistant. The possible mechanisms of LO antitumor activity through the key biochemical processes are discussed.