The condensation domain of surfactin A synthetase C variant 18b in space group P212121

Experimental Data Snapshot

  • Resolution: 1.93 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

wwPDB Validation   3D Report Full Report

Ligand Structure Quality Assessment 

This is version 1.1 of the entry. See complete history


High-throughput reprogramming of an NRPS condensation domain.

Folger, I.B.Frota, N.F.Pistofidis, A.Niquille, D.L.Hansen, D.A.Schmeing, T.M.Hilvert, D.

(2024) Nat Chem Biol 

  • DOI: https://doi.org/10.1038/s41589-023-01532-x
  • Primary Citation of Related Structures:  
    8F7F, 8F7G, 8F7H, 8F7I, 8FE1

  • PubMed Abstract: 

    Engineered biosynthetic assembly lines could revolutionize the sustainable production of bioactive natural product analogs. Although yeast display is a proven, powerful tool for altering the substrate specificity of gatekeeper adenylation domains in nonribosomal peptide synthetases (NRPSs), comparable strategies for other components of these megaenzymes have not been described. Here we report a high-throughput approach for engineering condensation (C) domains responsible for peptide elongation. We show that a 120-kDa NRPS module, displayed in functional form on yeast, can productively interact with an upstream module, provided in solution, to produce amide products tethered to the yeast surface. Using this system to screen a large C-domain library, we reprogrammed a surfactin synthetase module to accept a fatty acid donor, increasing catalytic efficiency for this noncanonical substrate >40-fold. Because C domains can function as selectivity filters in NRPSs, this methodology should facilitate the precision engineering of these molecular assembly lines.

  • Organizational Affiliation

    Laboratory of Organic Chemistry, ETH Zurich, Zurich, Switzerland.

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Surfactin synthetase461Bacillus subtilisMutation(s): 9 
Find proteins for Q08787 (Bacillus subtilis (strain 168))
Explore Q08787 
Go to UniProtKB:  Q08787
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ08787
Sequence Annotations
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GOL (Subject of Investigation/LOI)
Query on GOL

Download Ideal Coordinates CCD File 
C3 H8 O3
Experimental Data & Validation

Experimental Data

  • Resolution: 1.93 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.736α = 90
b = 83.722β = 90
c = 86.379γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
HKL-2000data scaling
HKL-2000data reduction
Cootmodel building

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment 

Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
Canadian Institutes of Health Research (CIHR)Canada178084

Revision History  (Full details and data files)

  • Version 1.0: 2023-11-22
    Type: Initial release
  • Version 1.1: 2024-02-21
    Changes: Database references