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Functional Characterization of 3‐Aminobenzoic Acid Adenylation Enzyme PctU and UDP‐ N ‐Acetyl‐ d ‐Glucosamine: 3‐Aminobenzoyl‐ACP Glycosyltransferase PctL in Pactamycin Biosynthesis
Author(s) -
Kudo Fumitaka,
Zhang Jiahao,
Sato Shusuke,
Hirayama Akane,
Eguchi Tadashi
Publication year - 2019
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.201900239
Subject(s) - adenylylation , aminocyclitol , glycosyltransferase , uridine diphosphate , chemistry , biosynthesis , stereochemistry , enzyme , uridine , transferase , biochemistry , acyl carrier protein , moiety , rna , antibiotics , aminoglycoside , gene
Pactamycin is an antibiotic produced by Streptomyces pactum with antitumor and antimalarial properties. Pactamycin has a unique aminocyclitol core that is decorated with 3‐aminoacetophenone, 6‐methylsaliciate, and an N , N ‐dimethylcarbamoyl group. Herein, we show that the adenylation enzyme PctU activates 3‐aminobenzoic acid (3ABA) with adenosine triphosphate and ligates it to the holo form of the discrete acyl carrier protein PctK to yield 3ABA‐PctK. Then, 3ABA‐PctK is N‐glycosylated with uridine diphosphate‐ N ‐acetyl‐ d ‐glucosamine (UDP‐GlcNAc) by the glycosyltransferase PctL to yield GlcNAc‐3ABA‐PctK. Because 3ABA is known to be a precursor of the 3‐aminoacetophenone moiety, PctU appears to be a gatekeeper that selects the appropriate 3‐aminobenzoate starter unit. Overall, we propose that acyl carrier protein‐bound glycosylated 3ABA derivatives are biosynthetic intermediates of pactamycin biosynthesis.