6U9I

Crystal structure of BvnE pinacolase from Penicillium brevicompactum

Summary for 6U9I

• Entry DOI: 10.2210/pdb6u9i/pdb
• Descriptor: BvnE, GLYCEROL, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: isomerase, pinacolase
• Biological source: Penicillium brevicompactum
• Total number of polymer chains: 2
• Total formula weight: 35348.20

Authors

Ye, Y.,Du, L.,Zhang, X.,Newmister, S.A.,McCauley, M.,Alegre-Requena, J.V.,Zhang, W.,Mu, S.,Minami, A.,Fraley, A.E.,Adrover-Castellano, M.L.,Carney, N.,Shende, V.V.,Oikawa, H.,Kato, H.,Tsukamoto, S.,Paton, R.S.,Williams, R.M.,Sherman, D.H.,Li, S. (deposition date: 2019-09-09, release date: 2020-09-09, Last modification date: 2023-10-11)

Primary citation

Ye, Y.,Du, L.,Zhang, X.,Newmister, S.A.,McCauley, M.,Alegre-Requena, J.V.,Zhang, W.,Mu, S.,Minami, A.,Fraley, A.E.,Adrover-Castellano, M.L.,Carney, N.A.,Shende, V.V.,Qi, F.,Oikawa, H.,Kato, H.,Tsukamoto, S.,Paton, R.S.,Williams, R.M.,Sherman, D.H.,Li, S.
Fungal-derived brevianamide assembly by a stereoselective semipinacolase.
Nat Catal, 3:497-506, 2020

PubMed Abstract: Fungal bicyclo[2.2.2]diazaoctane indole alkaloids represent an important family of natural products with a wide-spectrum of biological activities. Although biomimetic total syntheses of representative compounds have been reported, the details of their biogenesis, especially the mechanisms for assembly of diastereomerically distinct and enantiomerically antipodal metabolites, have remained largely uncharacterized. Brevianamide A represents a basic form of the sub-family bearing a dioxopiperazine core and a rare 3--ψ-indoxyl skeleton. Here, we identified the Brevianamide A biosynthetic gene cluster from NRRL 864 and elucidated the metabolic pathway. BvnE was revealed to be an essential isomerase/semi-pinacolase that specifies selective production of the natural product. Structural elucidation, molecular modeling, and mutational analysis of BvnE, and quantum chemical calculations provided mechanistic insights into the diastereoselective formation of the 3--ψ-indoxyl moiety in Brevianamide A. This occurs through a BvnE-controlled semi-pinacol rearrangement and a subsequent spontaneous intramolecular [4+2] -Diels-Alder cycloaddition.

PubMed: 32923978
DOI: 10.1038/s41929-020-0454-9

Experimental method

X-RAY DIFFRACTION (1.777 Å)