6J1M

Anisodus acutangulus type III polyketide sythase AaPKS2 in complex with 4-carboxy-3-oxobutanoyl covalent to C166

Summary for 6J1M

• Entry DOI: 10.2210/pdb6j1m/pdb
• Descriptor: A. acutangulus PKS2, 3-oxopentanedioic acid, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: anisodus acutangulus, type iii polyketide sythase, tropane alkaloids biosythesis, biosynthetic protein
• Biological source: Anisodus acutangulus
• Total number of polymer chains: 2
• Total formula weight: 93994.17

Authors

Fang, C.L.,Zhang, Y. (deposition date: 2018-12-28, release date: 2019-09-11, Last modification date: 2025-09-17)

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 (2.001 Å)