6J1N

Anisodus acutangulus type III polyketide sythase AaPKS2 in complex with 4-carboxy-3-oxobutanoyl-CoA

Summary for 6J1N

• Entry DOI: 10.2210/pdb6j1n/pdb
• Descriptor: A. acutangulus PKS2, (3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-10,14,19,21-tetraoxo-2,4,6-trioxa-18-thia-11,15-diaza-3,5-diphosphatricosan-23-oic acid 3,5-dioxide (non-preferred name) (3 entities in total)
• Functional Keywords: anisodus acutangulus, type iii polyketide sythase, tropane alkaloids biosynthesis, biosynthetic protein
• Biological source: Anisodus acutangulus
• Total number of polymer chains: 2
• Total formula weight: 95244.94

Authors

Fang, C.L.,Zhang, Y. (deposition date: 2018-12-28, release date: 2019-09-11, Last modification date: 2024-10-16)

Primary citation

Huang, J.P.,Fang, C.,Ma, X.,Wang, L.,Yang, J.,Luo, J.,Yan, Y.,Zhang, Y.,Huang, S.X.
Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation.
Nat Commun, 10:4036-4036, 2019

PubMed Abstract: The skeleton of tropane alkaloids is derived from ornithine-derived N-methylpyrrolinium and two malonyl-CoA units. The enzymatic mechanism that connects N-methylpyrrolinium and malonyl-CoA units remains unknown. Here, we report the characterization of three pyrrolidine ketide synthases (PYKS), AaPYKS, DsPYKS, and AbPYKS, from three different hyoscyamine- and scopolamine-producing plants. By examining the crystal structure and biochemical activity of AaPYKS, we show that the reaction mechanism involves PYKS-mediated malonyl-CoA condensation to generate a 3-oxo-glutaric acid intermediate that can undergo non-enzymatic Mannich-like condensation with N-methylpyrrolinium to yield the racemic 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This study therefore provides a long sought-after biosynthetic mechanism to explain condensation between N-methylpyrrolinium and acetate units and, more importantly, identifies an unusual plant type III polyketide synthase that can only catalyze one round of malonyl-CoA condensation.

PubMed: 31492848
DOI: 10.1038/s41467-019-11987-z

Experimental method

X-RAY DIFFRACTION (2.532 Å)