ExplorEnz: EC 2.1.1.390

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2.1.1.390

Accepted name:

gentamicin X2 methyltransferase

Reaction:

gentamicin X2 + 2 S-adenosyl-L-methionine + reduced acceptor = geneticin + 5′-deoxyadenosine + L-methionine + S-adenosyl-L-homocysteine + oxidized acceptor (overall reaction)
(1a) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin
(1b) methylcob(III)alamin + gentamicin X2 + S-adenosyl-L-methionine = cob(III)alamin + geneticin + 5′-deoxyadenosine + L-methionine
(1c) cob(III)alamin + reduced acceptor = cob(I)alamin + oxidized acceptor

Glossary:

geneticin = G418 = (1R,2S,3S,4R,6S)-4,6-diamino-3-{[3-deoxy-4-C-methyl-3-(methylamino)-β-L-arabinopyranosyl]oxy}-2-hydroxycyclohexyl 2-amino-2,7-dideoxy-D-glycero-α-D-gluco-heptopyranoside

Other name(s):

genK (gene name); gntK (gene name); gentamicin C-methyltransferase (ambiguous)

Systematic name:

S-adenosyl-L-methionine:gentamicin X2 C6′-methyltransferase

Comments:

The enzyme, isolated from the bacterium Micromonospora echinospora, has a single [4Fe-4S] cluster per monomer. It is a radical S-adenosyl-L-methionine (SAM) enzyme with a methylcob(III)alamin cofactor. The enzyme uses two molecues of SAM for the reaction. One molecule forms a 5′-deoxyadenosyl radical, while the other is used to methylate the cobalamin cofactor. It catalyses methylation of the 6′-carbon of gentamicin X2 (GenX2) to produce genetricin (G418) during the biosynthesis of gentamicins. The 6′-pro-R-hydrogen atom of GenX2 is stereoselectively abstracted by the 5′-deoxyadenosyl radical and methylation occurs with retention of configuration at C⁶′. The regeneration of cob(I)alamin from cob(III)alamin is carried out with an as yet unidentified electron donor.

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Kim, J.Y., Suh, J.W., Kang, S.H., Phan, T.H., Park, S.H. and Kwon, H.J. Gene inactivation study of gntE reveals its role in the first step of pseudotrisaccharide modifications in gentamicin biosynthesis. Biochem. Biophys. Res. Commun. 372 (2008) 730–734. [DOI] [PMID: 18533111]
2.	Hong, W. and Yan, L. Identification of gntK, a gene required for the methylation of purpurosamine C-6′ in gentamicin biosynthesis. J. Gen. Appl. Microbiol. 58 (2012) 349–356. [DOI] [PMID: 23149679]
3.	Kim, H.J., McCarty, R.M., Ogasawara, Y., Liu, Y.N., Mansoorabadi, S.O., LeVieux, J. and Liu, H.W. GenK-catalyzed C-6′ methylation in the biosynthesis of gentamicin: isolation and characterization of a cobalamin-dependent radical SAM enzyme. J. Am. Chem. Soc. 135 (2013) 8093–8096. [DOI] [PMID: 23679096]
4.	Kim, H.J., Liu, Y.N., McCarty, R.M. and Liu, H.W. Reaction Catalyzed by GenK, a Cobalamin-Dependent Radical S-Adenosyl-l-methionine Methyltransferase in the Biosynthetic Pathway of Gentamicin, Proceeds with Retention of Configuration. J. Am. Chem. Soc. 139 (2017) 16084–16087. [DOI] [PMID: 29091410]

[EC 2.1.1.390 created 2023]