Modification of aklavinone and aclacinomycins in vitro and in vivo by rhodomycin biosynthesis gene products.
The rdm genes B, C and E from Streptomyces purpurascens encode enzymes that tailor aklavinone and aclacinomycins. We report that in addition to hydroxylation of aklavinone to epsilon-rhodomycinone, RdmE (aklavinone-11-hydroxylase) hydroxylated 11-deoxy-beta-rhodomycinone to beta-rhodomycinone both in vivo and in vitro. 15-Demethoxyaklavinone and decarbomethoxyaklavinone did not serve as substrates. RdmC (aclacinomycin methyl esterase) converted aclacinomycin T (AcmT) to 15-demethoxyaclacinomycin T, which was in turn converted to 10-decarbomethoxyaclacinomycin T and then to rhodomycin B by RdmB (aclacinomycin-10-hydroxylase). RdmC and RdmB were most active on AcmT, the one-sugar derivative, with their activity decreasing by 70-90% on two- and three-sugar aclacinomycins. Aclacinomycin A competitively inhibited the AcmT modifications at C-10. The results presented here suggest that in vivo the modifications at C-10 take place principally after addition of the first sugar.
Wang
Yulong
Y
Department of Biochemistry and Food Chemistry, University of Turku, FIN-20014, Turku, Finland.
Niemi
Jarmo
J
Mäntsälä
Pekka
P
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D018943:Anthracyclines / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009279:Naphthacenes / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D013379:Substrate Specificity
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D009279:Naphthacenes; C011157:aclacinomycins; C004977:rhodomycin; C027832:aklavinone; D015250:Aclarubicin; D006899:Mixed Function Oxygenases; C414540:aclacinomycin-10-hydroxylase; C090407:aklavinone 11-hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D002265:Carboxylic Ester Hydrolases; C414541:aclacinomycin methyl esterase