| abstract |
Described is a new enzyme, 31-O-desmethyl-FK-506 O-methyltransferase (FKMT) and its N-terminal amino acid sequence. This enzyme can specifically and preferentially methylate the C-31 hydroxy group in 31-O-desmethyl FK-506/FR-900506 and other 31-O-desmethyl analogs of FK-506/FR-900506 and related compounds such as 31-O-desmethyl immunomycin type molecules, also designated FK-520 and FR-900520 by Fujisawa. The enzyme can be isolated from a FK-506 producing microorganism Streptomyces sp. (Merck Culture Collection No. MA 6858) ATCC No. 55098. Employing the enzyme in its active form, supplemented with Mg+2 ion, in the presence of the methyl donor, S-adenosyl methionine (SAM), derivatives of 31-O-desmethyl FK-506, 31-O-desmethyl FK-520 and related 31-O-desmethyl compounds may be prepared. |