8S1Y

ThaOS V79A

This is a non-PDB format compatible entry.

Summary for 8S1Y

• Entry DOI: 10.2210/pdb8s1y/pdb
• Descriptor: 8-amino-7-oxononanoate synthase/2-amino-3-ketobutyrate coenzyme A ligase, (4S)-2-METHYL-2,4-PENTANEDIOL, (2~{R},4~{R})-5,5-dimethyl-2-[2-methyl-3-oxidanyl-5-(phosphonooxymethyl)pyridin-4-yl]-1,3-thiazolidine-4-carboxylic acid, ... (4 entities in total)
• Functional Keywords: alpha-oxoamine synthase; plp; l-penicillamine; thermophilic; synthase; biocatalyst, ligase
• Biological source: Thermus thermophilus
• Total number of polymer chains: 2
• Total formula weight: 94579.91

Authors

Basle, A.,Ashley, B.,Campopiano, D.J.,Marles-wright, J. (deposition date: 2024-02-16, release date: 2025-03-05, Last modification date: 2025-09-24)

Primary citation

Ashley, B.,Mathew, S.,Sajjad, M.,Zhu, Y.,Novikovs, N.,Basle, A.,Marles-Wright, J.,Campopiano, D.J.
Rational engineering of a thermostable alpha-oxoamine synthase biocatalyst expands the substrate scope and synthetic applicability.
Commun Chem, 8:78-78, 2025

PubMed Abstract: Carbon-carbon bond formation is one of the key pillars of organic synthesis. Green, selective and efficient biocatalytic methods for such are therefore highly desirable. The α-oxoamine synthases (AOSs) are a class of pyridoxal 5'-phosphate (PLP)-dependent, irreversible, carbon-carbon bond-forming enzymes, which have been limited previously by their narrow substrate specificity and requirement of acyl-CoA thioester substrates. We recently characterized a thermophilic enzyme from Thermus thermophilus (ThAOS) with a much broader substrate scope and described its use in a chemo-biocatalytic cascade process to generate pyrroles in good yields and timescales. Herein, we report the structure-guided engineering of ThAOS to arrive at variants able to use a greatly expanded range of amino acid and simplified N-acetylcysteamine (SNAc) acyl-thioester substrates. The crystal structure of the improved ThAOS V79A variant with a bound PLP:L-penicillamine external aldimine ligand, provides insight into the properties of the engineered biocatalyst.

PubMed: 40082705
DOI: 10.1038/s42004-025-01448-8

Experimental method

X-RAY DIFFRACTION (1.5 Å)