9J56

Functional Investigation of the SAM-Dependent Methyltransferases Rdmb in Anthracycline Biosynthesis

This is a non-PDB format compatible entry.

Summary for 9J56

• Entry DOI: 10.2210/pdb9j56/pdb
• Descriptor: Aclacinomycin 10-hydroxylase RdmB, S-ADENOSYL-L-HOMOCYSTEINE, (7~{S},9~{S})-7-[(2~{R},4~{S},5~{S},6~{S})-4-azanyl-6-methyl-5-oxidanyl-oxan-2-yl]oxy-9-ethyl-4-methoxy-6,9,11-tris(oxidanyl)-8,10-dihydro-7~{H}-tetracene-5,12-dione, ... (4 entities in total)
• Functional Keywords: methyltransferase domain-containing protein, rdmb, transferase
• Biological source: Streptomyces purpurascens
• Total number of polymer chains: 2
• Total formula weight: 81471.78

Authors

Yang, Q.Y.,Sang, M.L.,Zhang, W. (deposition date: 2024-08-11, release date: 2024-11-06)

Primary citation

Sang, M.,Yang, Q.,Guo, J.,Feng, P.,Ma, W.,Zhang, W.
Functional investigation of the SAM-dependent methyltransferase RdmB in anthracycline biosynthesis.
Synth Syst Biotechnol, 10:102-109, 2025

PubMed Abstract: A novel sub-class of -adenosyl-l-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines. Exemplified by RdmB from it was found with 10-decarboxylative hydroxylation activity on anthracyclines. We herein investigated the catalytic activities of RdmB and discovered a previously unknown 4--methylation activity. The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hydroxylation and 4--methylation, respectively, which define two distinct catalytic centers in RdmB. Furthermore, the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.

PubMed: 39308748
DOI: 10.1016/j.synbio.2024.09.002

Experimental method

X-RAY DIFFRACTION (2.1 Å)