Structural highlights
FunctionPublication Abstract from PubMedX-type actinomycins (Acms) contain 4-hydroxyproline (Acm X0) or 4-oxoproline (Acm X2) in their ss-pentapeptide lactone rings whereas their alpha-ring contains proline. We demonstrate that these Acms are formed through asymmetric condensation of Acm half molecules (Acm halves) containing proline with 4-hydroxyproline- or 4-oxo-proline-containing Acm halves. In turn we show - using an artificial Acm half analogue (PPL 1) with proline in its peptide chain - its conversion into the 4-hydroxyproline and 4-oxoproline-containing Acm halves, PPL 0 and PPL 2, in mycelial suspensions of Streptomyces antibioticus. Two responsible genes of the Acm X biosynthetic gene cluster of S. antibioticus, saacmM and saacmN, encoding a cytochrome P450 monooxygenase and a ferredoxin, were identified. After co-expression in Escherichia coli their gene products converted PPL 1 into PPL 1 and PPL 2 in vivo as well as in situ in permeabilized cell of the transformed E. coli strain in conjunction with the host-encoded ferredoxin reductase in a NADH (NADPH)-dependent manner.saAcmM has high sequence similarity to the Cyp107Z (Ema) family of cytochrome P450s monooxygenases which can convert avermectin B1 into its keto derivative 4-oxo-avermectin B1. Determination of the structure of saAcmM revealed high similarity to the Ema structure but with significant differences in residues decorating their active sites, which defines saAcmM and its orthologues as a distinct new family of peptidylproline-ketonizing Cyps. Ketonization of proline residues in the peptide chains of actinomycins by a 4-Oxoproline synthase.,Semsary S, Crnovcic I, Driller R, Vater J, Loll B, Keller U Chembiochem. 2018 Jan 12. doi: 10.1002/cbic.201700666. PMID:29327817[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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