5O15

Crystal structure of bifunctional dehydratase-cyclase domain in ambruticin biosynthesis

Summary for 5O15

• Entry DOI: 10.2210/pdb5o15/pdb
• Descriptor: AmbC, GLYCEROL (3 entities in total)
• Functional Keywords: biocatalysis, cyclases, dehydratases, heterocycles, polyketides, double hotdog fold, lyase
• Biological source: Sorangium cellulosum
• Total number of polymer chains: 2
• Total formula weight: 64366.31

Authors

Sung, K.H.,Berkhan, G.,Hollmann, T.,Wagner, L.,Hahn, F.,Blankenfeldt, W. (deposition date: 2017-05-18, release date: 2017-11-08, Last modification date: 2024-01-17)

Primary citation

Sung, K.H.,Berkhan, G.,Hollmann, T.,Wagner, L.,Blankenfeldt, W.,Hahn, F.
Insights into the Dual Activity of a Bifunctional Dehydratase-Cyclase Domain.
Angew. Chem. Int. Ed. Engl., 57:343-347, 2018

PubMed Abstract: Oxygen-containing heterocycles are a common structural motif in polyketide natural products and contribute significantly to their biological activity. Here, we report structural and mechanistic investigations on AmbDH3, a polyketide synthase domain with dual activity as dehydratase (DH) and pyran-forming cyclase in ambruticin biosynthesis. AmbDH3 is similar to monofunctional DH domains, using H51 and D215 for dehydration. V173 was confirmed as a diagnostic residue for cyclization activity by a mutational study and enzymatic in vitro experiments. Similar motifs were observed in the seemingly monofunctional AmbDH2, which also shows an unexpected cyclase activity. Our results pave the way for mining of hidden cyclases in biosynthetic pathways. They also open interesting prospects for the generation of novel biocatalysts for chemoenzymatic synthesis and pyran-polyketides by combinatorial biosynthesis.

PubMed: 29084363
DOI: 10.1002/anie.201707774

Experimental method

X-RAY DIFFRACTION (1.174 Å)