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Title: The role of OleA His285 in orchestration of long-chain acyl-coenzyme A substrates

Abstract

Renewable production of hydrocarbons is being pursued as a petroleum-independent source of commodity chemicals and replacement for biofuels. The bacterial biosynthesis of long-chain olefins represents one such platform. The process is initiated by OleA catalyzing the condensation of two fatty acyl-coenzyme A substrates to form a β-keto acid.In this work, the mechanistic role of the conserved His285 is investigated through mutagenesis, activity assays, and X-ray crystallography. Our data demonstrate that His285 is required for product formation, influences the thiolase nucleophile Cys143 and the acyl-enzyme intermediate before and after transesterification, and orchestrates substrate coordination as a defining component of an oxyanion hole. As a consequence, His285 plays a key role in enabling a mechanistic strategy in OleA that is distinct from other thiolases.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Univ. of Minnesota, St. Paul, MN (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Cancer Institute (NCI); National Institute of General Medical Sciences (NIGMS); The BioTechnology Institute, University of Minnesota; National Institutes of Health (NIH); University of Minnesota Doctoral Dissertation Fellowship
OSTI Identifier:
1434717
Grant/Contract Number:  
AC02-06CH11357; ACB-12002; AGM-12006; 1000014885 10866 MNT11; T32GM008700; T32GM008347
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
FEBS Letters
Additional Journal Information:
Journal Volume: 592; Journal Issue: 6; Journal ID: ISSN 0014-5793
Publisher:
Federation of European Biochemical Societies
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; OleA; thiolase; X-ray crystallography

Citation Formats

Jensen, Matthew R., Goblirsch, Brandon R., Esler, Morgan A., Christenson, James K., Mohamed, Fatuma A., Wackett, Lawrence P., and Wilmot, Carrie M. The role of OleA His285 in orchestration of long-chain acyl-coenzyme A substrates. United States: N. p., 2018. Web. doi:10.1002/1873-3468.13004.
Jensen, Matthew R., Goblirsch, Brandon R., Esler, Morgan A., Christenson, James K., Mohamed, Fatuma A., Wackett, Lawrence P., & Wilmot, Carrie M. The role of OleA His285 in orchestration of long-chain acyl-coenzyme A substrates. United States. doi:10.1002/1873-3468.13004.
Jensen, Matthew R., Goblirsch, Brandon R., Esler, Morgan A., Christenson, James K., Mohamed, Fatuma A., Wackett, Lawrence P., and Wilmot, Carrie M. Sun . "The role of OleA His285 in orchestration of long-chain acyl-coenzyme A substrates". United States. doi:10.1002/1873-3468.13004. https://www.osti.gov/servlets/purl/1434717.
@article{osti_1434717,
title = {The role of OleA His285 in orchestration of long-chain acyl-coenzyme A substrates},
author = {Jensen, Matthew R. and Goblirsch, Brandon R. and Esler, Morgan A. and Christenson, James K. and Mohamed, Fatuma A. and Wackett, Lawrence P. and Wilmot, Carrie M.},
abstractNote = {Renewable production of hydrocarbons is being pursued as a petroleum-independent source of commodity chemicals and replacement for biofuels. The bacterial biosynthesis of long-chain olefins represents one such platform. The process is initiated by OleA catalyzing the condensation of two fatty acyl-coenzyme A substrates to form a β-keto acid.In this work, the mechanistic role of the conserved His285 is investigated through mutagenesis, activity assays, and X-ray crystallography. Our data demonstrate that His285 is required for product formation, influences the thiolase nucleophile Cys143 and the acyl-enzyme intermediate before and after transesterification, and orchestrates substrate coordination as a defining component of an oxyanion hole. As a consequence, His285 plays a key role in enabling a mechanistic strategy in OleA that is distinct from other thiolases.},
doi = {10.1002/1873-3468.13004},
journal = {FEBS Letters},
issn = {0014-5793},
number = 6,
volume = 592,
place = {United States},
year = {2018},
month = {2}
}

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