Alpha-N-dichloroacetyl-p-aminophenylserinol N-oxygenase (CmlI) (CmlI)

CmlI is a non-heme diiron oxygenase that plays a critical role in the biosynthesis of the broad-spectrum antibiotic chloramphenicol in Streptomyces venezuelae [1, 2, 4]. It specifically catalyzes the final six-electron oxidation of the arylamine precursor, d-threo-1-(4-aminophenyl)-2-dichloroacetylamino-1,3-propanediol (NH2-CAM), to the arylnitro group found in the active antibiotic [1, 3, 5]. The enzyme's active site contains a (hydr)oxo- and carboxylate-bridged dinuclear iron cluster, which activates molecular oxygen to form a stable diferric-peroxo intermediate [1, 10, 41]. This intermediate facilitates the sequential oxygenation steps—converting the amine to a hydroxylamine, then to a nitroso group, and finally to the nitro group—without the dissociation of intermediates from the active site [3, 5, 48]. CmlI is a member of the heme oxygenase-like metalloenzyme (HDO) superfamily and is a subject of interest for its unique catalytic mechanism and potential applications in biocatalysis and the engineering of novel nitro-containing natural products [37, 39, 41]. The enzyme is notable for its ability to perform multiple oxidation steps within a single active site, preserving efficiency and specificity while avoiding the release of reactive intermediates [3, 5]. Structural studies have revealed a four-helix bundle fold that coordinates the diiron cluster, similar to other oxygen-activating enzymes like methane monooxygenase [2, 34, 38]. While not a direct therapeutic target in humans, CmlI and its homologs in pathogenic bacteria are studied for their roles in secondary metabolism and as potential targets for novel antimicrobial strategies [31, 35]. Its unique peroxo intermediate structure distinguishes it from other diiron enzymes, providing insights into the diverse ways nature activates oxygen for complex chemical transformations [41, 48].

Other names

Arylamine oxygenase CmlIN-oxygenase CmlIChloramphenicol biosynthesis N-oxygenaseNon-heme di-iron N-oxygenaseArylamine N-oxygenase

Catalyzes the six-electron oxidation of an arylamine precursor to an arylnitro group via hydroxylamine and nitroso intermediates using a non-heme diiron cluster and molecular oxygen.