Aclacinomycin 10-hydroxylase (RdmB)

Aclacinomycin-10-hydroxylase (RdmB) is a methyltransferase homolog that catalyzes a S-adenosyl-L-methionine (SAM)-dependent hydroxylation of the C-10 carbon atom in 15-demethoxy-epsilon-rhodomycin, an essential step in the biosynthesis of the polyketide antibiotics beta-rhodomycin and aclacinomycin. Unlike typical methyltransferases, it does not transfer a methyl group but instead hydroxylates the substrate using molecular oxygen; its active site structure is evolved for this function. This enzyme is functionally and structurally unique among methyltransferase family enzymes, as it lacks methyltransferase activity due to unfavorable AdoMet orientation. Its action is critical for producing anthracyclines—anti-tumor antibiotics used in chemotherapy. Structural studies reveal that it operates as a tetramer and uses unique substrate-induced conformational changes to close the active site over bound anthracycline intermediates

Other names

RdmBAclacinomycin-10-hydroxylaseMethyltransferase homolog

For its role in drug biosynthesis: SAM-dependent hydroxylation mechanism—utilizes S-adenosyl-L-methionine as a cofactor for substrate-assisted hydroxylation at the C-10 position of anthracycline precursors. SAM analogue sinefungin can also serve as cofactor; S-adenosyl-L-homocysteine is an inhibitor