6J32

Crystal Structure Analysis of the Glycotransferase of kitacinnamycin

6J32 の概要

• エントリーDOI: 10.2210/pdb6j32/pdb
• 分子名称: Kcn28 (2 entities in total)
• 機能のキーワード: glycotransferase, biosynthetic protein
• 由来する生物種: Kitasatospora
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 174477.72

構造登録者

Shi, J.,Liu, C.L.,Zhang, B.,Guo, W.J.,Zhu, J.P.,Xu, X.,Xu, Q.,Jiao, R.H.,Tan, R.X.,Ge, H.M. (登録日: 2019-01-03, 公開日: 2020-01-15, 最終更新日: 2023-11-22)

主引用文献

Shi, J.,Liu, C.L.,Zhang, B.,Guo, W.J.,Zhu, J.,Chang, C.Y.,Zhao, E.J.,Jiao, R.H.,Tan, R.X.,Ge, H.M.
Genome mining and biosynthesis of kitacinnamycins as a STING activator.
Chem Sci, 10:4839-4846, 2019

PubMed Abstract: Cinnamoyl-containing nonribosomal peptides (CCNPs) are a small group of secondary metabolites with potent biological activities produced by actinobacteria. Two remarkable features in the biosynthesis of CCNPs include the nonribosomal peptide synthases (NRPSs) for assembly of the depsipeptide backbone and the type II polyketide synthases (PKSs) for N-terminal cinnamoyl moiety construction. Here, we present a genome mining approach targeting both NRPS and type II PKS for discovery of new CCNPs, which led to the identification of 51 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named kitacinnamycins, one of which showing potent activation ability towards the stimulator of interferon genes (STING) protein, was identified. Bioinformatic, genetic and biochemical analysis revealed the use of the NRPS assembly line to form the macrocyclic peptide backbone, followed by a P450 monooxygenase to generate terminal oxidized groups. A glycosyltransferase with relatively broad substrate specificity transfers sugars to the newly generated OH/COOH group. The protein crystallographic study further provided structural insights into this glycosylation. Our results not only demonstrated the feasibility of genome mining and strain prioritization for the discovery of new bioactive natural products but also disclosed the biosynthetic pathway for kitacinnamycins.

PubMed: 31160959
DOI: 10.1039/c9sc00815b

実験手法

X-RAY DIFFRACTION (2.5 Å)