6SKX

Structure of Reductive Aminase from Neosartorya fumigata


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases.

Mangas-Sanchez, J.Sharma, M.Cosgrove, S.C.Ramsden, J.I.Marshall, J.R.Thorpe, T.W.Palmer, R.B.Grogan, G.Turner, N.J.

(2020) Chem Sci 11: 5052-5057

  • DOI: https://doi.org/10.1039/d0sc02253e
  • Primary Citation of Related Structures:  
    6SKX, 6SLE

  • PubMed Abstract: 

    Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms from Neosartorya spp. ( Nf RedAm and Nfis RedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14 000 as well as continous flow reactions, obtaining chiral amines such as ( R )-2-aminohexane in space time yields up to 8.1 g L -1 h -1 . The remarkable features of Nf RedAm and Nfis RedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis.


  • Organizational Affiliation

    School of Chemistry, University of Manchester, Manchester Institute of Biotechnology 131 Princess Street Manchester M1 7DN UK nicholas.turner@manchester.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Oxidoreductase, putative285Aspergillus fumigatus Af293Mutation(s): 0 
Gene Names: AFUA_5G01250
EC: 1.1.1.31
UniProt
Find proteins for Q4WDZ8 (Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293))
Explore Q4WDZ8 
Go to UniProtKB:  Q4WDZ8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ4WDZ8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 114α = 90
b = 114β = 90
c = 60γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Biotechnology and Biological Sciences Research CouncilUnited KingdomBB/M006832/1

Revision History  (Full details and data files)

  • Version 1.0: 2020-06-24
    Type: Initial release
  • Version 1.1: 2021-07-07
    Changes: Database references
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Refinement description