A dissected non-ribosomal peptide synthetase maintains activity.

Autor: Platt AJ; Department of Microbiology and Immunology, Institute of Molecular Medicine and Infectious Disease, Center for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA., Padrick S; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N 15(th) Street, Philadelphia, PA 19102, USA., Ma AT; Department of Microbiology and Immunology, Institute of Molecular Medicine and Infectious Disease, Center for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA., Beld J; Department of Microbiology and Immunology, Institute of Molecular Medicine and Infectious Disease, Center for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: jb3669@drexel.edu.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Proteins and proteomics [Biochim Biophys Acta Proteins Proteom] 2024 Jan 01; Vol. 1872 (1), pp. 140972. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1016/j.bbapap.2023.140972
Abstrakt: Non-ribosomal peptide synthetases (NRPSs) generate chemically complex compounds and their modular architecture suggests that changing their domain organization can predictably alter their products. Ebony, a small three-domain NRPS, catalyzes the formation of β-alanine containing amides from biogenic amines. To examine the necessity of interdomain interactions, we modeled and docked domains of Ebony to reveal potential interfaces between them. Testing the same domain combinations in vitro showed that 8 % of activity was preserved after Ebony was dissected into a di-domain and a detached C-terminal domain, suggesting that sufficient interaction was maintained after dissection. Our work creates a model to identify domain interfaces necessary for catalysis, an important step toward utilizing Ebony as a combinatorial engineering platform for novel amides.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joris Beld reports financial support was provided by Commonwealth Universal Research Enhancement (CURE) grant.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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