9AZA

Crystal structure of LolTv4

Summary for 9AZA

• Entry DOI: 10.2210/pdb9aza/pdb
• Related: 8DL5
• Descriptor: Aminotransferase, class V/Cysteine desulfurase, PYRIDOXAL-5'-PHOSPHATE (2 entities in total)
• Functional Keywords: mannichase, biosynthetic protein
• Biological source: Penicillium expansum
• Total number of polymer chains: 1
• Total formula weight: 53189.55

Authors

Gao, J.,Hai, Y. (deposition date: 2024-03-10, release date: 2024-07-17, Last modification date: 2024-08-07)

Primary citation

Liu, S.,Gao, J.,Zou, Y.,Hai, Y.
Enzymatic Synthesis of Unprotected alpha , beta-Diamino Acids via Direct Asymmetric Mannich Reactions.
J.Am.Chem.Soc., 146:20263-20269, 2024

PubMed Abstract: α,β-Diamino acids are important structural motifs and building blocks for numerous bioactive natural products, peptidomimetics, and pharmaceuticals, yet efficient asymmetric synthesis to access these stereoarrays remains a challenge. Herein, we report the development of a pyridoxal 5'-phosphate (PLP)-dependent enzyme that is engineered to catalyze stereoselective Mannich-type reactions between free α-amino acids and enolizable cyclic imines. This biocatalyst enabled one-step asymmetric enzymatic synthesis of the unusual pyrrolidine-containing amino acid L-tambroline at gram-scale with high enantio- and diastereocontrol. Furthermore, this enzymatic platform is capable of utilizing a diverse range of α-amino acids as the Mannich donor and various cyclic imines as the acceptor. By coupling with different imine-generating enzymes, we established versatile biocatalytic cascades and demonstrated a general, concise, versatile, and atom-economic approach to access unprotected α,β-diamino acids, including structurally complex α,α-disubstituted α,β-diamino acids with contiguous stereocenters.

PubMed: 39001849
DOI: 10.1021/jacs.4c05581

Experimental method

X-RAY DIFFRACTION (2.84 Å)