An FAD-requiring monooxygenase active on tetracycline antibiotic and some of its derivatives, which leads to their inactivation (PubMed:26097034). Expression in E.coli confers high resistance to tetracycline and oxytetracycline, does not confer resistance to minocycline or tigecycline. The reaction requires NADPH (PubMed:26097034). Expression in L.pneumophila confers resistance to tetracycline (PubMed:28481346). Degrades and confers resistance to tetracycline and chlortetracycline (PubMed:26097034, PubMed:28481346). a tetracycline + H(+) + NADPH + O2 = a (1S,10aS)-3-(CONH2)-1-(Me2N)-3,3a,4,6-(HO)4-2,5-dioxo-1H,10aH,11H,11aH-cyclopenta[b]anthracene + CO + H2O + NADP(+) 7-chlorotetracycline + H(+) + NADPH + O2 = (1S,10S,10aS)-3-(CONH2)-9-Cl-1-(Me2N)-3,3a,4,10-(HO)4-10-Me-2,5-dioxo-1H,10aH,11H,11aH-cyclopenta[b]anthracen-6-olate + CO + H2O + NADP(+) Binds 1 FAD per subunit. Inhibited by anhydrotetracycline. kcat for tetracycline is 6.4 min(-1), kcat for chlortetracycline is 6.6 min(-1). Consists of an N-terminal FAD-binding domain with a Rossman fold, a substrate-binding domain and a C-terminal helix that bridges the 2 domains close to the antibiotic-binding site. This last helix is flexible, is not found in TetX of Bacteroides species, and may contribute to their different substrate specificities. Increase in bacterial tetracycline sensitivity. Tetracycline antibiotics bind to the ribosomal acceptor site (A-site), preventing binding of the aminoacyl-tRNA to the A-site. The hydrophilic side of tetracycline makes many hydrogen-bonding interactions with oxygen atoms of the ribosome's phosphate backbone. Belongs to the aromatic-ring hydroxylase family.