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NAD + ‐Dependent Dehydrogenase PctP and Pyridoxal 5′‐Phosphate Dependent Aminotransferase PctC Catalyze the First Postglycosylation Modification of the Sugar Intermediate in Pactamycin Biosynthesis
Author(s) -
Hirayama Akane,
Chu Jinmiao,
Goto Ena,
Kudo Fumitaka,
Eguchi Tadashi
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700483
Subject(s) - biosynthesis , biochemistry , chemistry , dehydrogenase , nad+ kinase , enzyme , stereochemistry , glycosylation , pyridoxal , sugar phosphates , amino acid , moiety
The unique five‐membered aminocyclitol core of the antitumor antibiotic pactamycin originates from d ‐glucose, so unprecedented enzymatic modifications of the sugar intermediate are involved in the biosynthesis. However, the order of the modification reactions remains elusive. Herein, we examined the timing of introduction of an amino group into certain sugar‐derived intermediates by using recombinant enzymes that were encoded in the pactamycin biosynthesis gene cluster. We found that the NAD + ‐dependent alcohol dehydrogenase PctP and pyridoxal 5′‐phosphate dependent aminotransferase PctC converted N ‐acetyl‐ d ‐glucosaminyl‐3‐aminoacetophonone into 3′‐amino‐3′‐deoxy‐ N ‐acetyl‐ d ‐glucosaminyl‐3‐aminoacetophenone. Further, N ‐acetyl‐ d ‐glucosaminyl‐3‐aminophenyl‐β‐oxopropanoic acid ethyl ester was converted into the corresponding 3′‐amino derivative. However, PctP did not oxidize most of the tested d ‐glucose derivatives, including UDP‐GlcNAc. Thus, modification of the GlcNAc moiety in pactamycin biosynthesis appears to occur after the glycosylation of aniline derivatives.