Biomedicines | |
KasQ an Epimerase Primes the Biosynthesis of Aminoglycoside Antibiotic Kasugamycin and KasF/H Acetyltransferases Inactivate Its Activity | |
Saeid Malek Zadeh1  Kuan-Hung Lin1  Tsung-Lin Li1  Zhe-Chong Wang1  Yung-Lin Wang1  R. Sidick Basha1  Jin-Ping Lin1  Rajesh Rattinam1  Ning-Shian Hsu1  Kamal Adhikari1  | |
[1] Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; | |
关键词: kasugamycin; kasugamine; antibiotic biosynthesis; epimerase and acetyltransferase; | |
DOI : 10.3390/biomedicines10020212 | |
来源: DOAJ |
【 摘 要 】
Kasugamycin (KSM), an aminoglycoside antibiotic, is composed of three chemical moieties: D-chiro-inositol, kasugamine and glycine imine. Despite being discovered more than 50 years ago, the biosynthetic pathway of KSM remains an unresolved puzzle. Here we report a structural and functional analysis for an epimerase, KasQ, that primes KSM biosynthesis rather than the previously proposed KasF/H, which instead acts as an acetyltransferase, inactivating KSM. Our biochemical and biophysical analysis determined that KasQ converts UDP-GlcNAc to UDP-ManNAc as the initial step in the biosynthetic pathway. The isotope-feeding study further confirmed that 13C, 15N-glucosamine/UDP-GlcNH2 rather than glucose/UDP-Glc serves as the direct precursor for the formation of KSM. Both KasF and KasH were proposed, respectively, converting UDP-GlcNH2 and KSM to UDP-GlcNAc and 2-N’-acetyl KSM. Experimentally, KasF is unable to do so; both KasF and KasH are instead KSM-modifying enzymes, while the latter is more specific and reactive than the former in terms of the extent of resistance. The information gained here lays the foundation for mapping out the complete KSM biosynthetic pathway.
【 授权许可】
Unknown