Modification of aklavinone and aclacinomycins in vitro and in vivo by rhodomycin biosynthesis gene products

: Wang YL, Niemi J, Mantsala P

Publisher: ELSEVIER SCIENCE BV

: 2002

: FEMS Microbiology Letters

: FEMS MICROBIOLOGY LETTERS

: FEMS MICROBIOL LETT

: 208

: 1

: 117

: 122

: 6

: 0378-1097

DOI: https://doi.org/10.1111/j.1574-6968.2002.tb11070.x

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. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.