6J32

Crystal Structure Analysis of the Glycotransferase of kitacinnamycin

Summary for 6J32

• Entry DOI: 10.2210/pdb6j32/pdb
• Descriptor: Kcn28 (2 entities in total)
• Functional Keywords: glycotransferase, biosynthetic protein
• Biological source: Kitasatospora
• Total number of polymer chains: 4
• Total formula weight: 174477.72

Authors

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. (deposition date: 2019-01-03, release date: 2020-01-15, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)