Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Structural and biochemical characterization of carrier proteins interacting with non-elongating ketosynthase from enacyloxin polyketide synthase

Tools
- Tools
+ Tools

Svatoš, Alma (2019) Structural and biochemical characterization of carrier proteins interacting with non-elongating ketosynthase from enacyloxin polyketide synthase. PhD thesis, University of Warwick.

[img]
Preview
PDF
WRAP_Theses_Svatos_2019.pdf - Submitted Version - Requires a PDF viewer.

Download (10Mb) | Preview
Official URL: http://webcat.warwick.ac.uk/record=b3714385~S15

Request Changes to record.

Abstract

Enacyloxin is an antibiotic synthesized inside bacterial cells by gigantic modular multienzyme complex called polyketide synthase (PKS), which is active against multidrug-resistant Acinetobacter baumannii that leads the World Health Organization ‘priority pathogens’ list. In spite of its promising physiological activity, enacyloxin IIa has not been used as a drug due its structural instability. The modular nature of enacyloxin and other PKSs makes them amenable to rational engineering to elucidating protein-protein interactions within PKSs will be crucial for their bioengineering to produce novel drugs. A key step in enacyloxin biosynthesis is the transfer of the polyketide chain from an acyl carrier protein (ACP) domain in the last PKS module to a standalone peptidyl carrier protein (PCP) by a non-elongating ketosynthase (KS^0) domain. It has been reported that this transfer is necessary for the condensation (C) domain to catalyse polyketide chain release via intermolecular esterification with 3, 4-dihydroxycyclo-hexane carboxylic acid (DHCCA). No esterification occurs when the substrate is attached to the ACP domain. Thus, the KS^0 transfers the substrate from a carrier protein that is unable to interact with the C domain to one that it is able to interact with.

An experimental approach combining NMR and biochemical techniques presented in the thesis suggests that the length of helix 1 and the lack of charged residues in the C-terminal part of ACP prevent it from establishing favourable interaction with C domain.

Item Type: Thesis or Dissertation (PhD)
Subjects: Q Science > QD Chemistry
Q Science > QP Physiology
R Medicine > RM Therapeutics. Pharmacology
Library of Congress Subject Headings (LCSH): Antibiotics -- Development, Antibiotics -- Synthesis, Carrier proteins, Polyketides, Biosynthesis, Natural products -- Biotechnology
Official Date: 30 September 2019
Dates:
DateEvent
30 September 2019UNSPECIFIED
Institution: University of Warwick
Theses Department: Department of Chemistry
Thesis Type: PhD
Publication Status: Unpublished
Supervisor(s)/Advisor: Lewandowski, Józef R. ; Challis, Gregory L.
Sponsors: European Research Council
Format of File: pdf
Extent: viii, 160 leaves : illustrations (some colour)
Language: eng

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us