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A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation
Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the ac...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460268/ https://www.ncbi.nlm.nih.gov/pubmed/34490847 http://dx.doi.org/10.7554/eLife.70067 |
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author | Patil, Gajanan S Kinatukara, Priyadarshan Mondal, Sudipta Shambhavi, Sakshi Patel, Ketan D Pramanik, Surabhi Dubey, Noopur Narasimhan, Subhash Madduri, Murali Krishna Pal, Biswajit Gokhale, Rajesh S Sankaranarayanan, Rajan |
author_facet | Patil, Gajanan S Kinatukara, Priyadarshan Mondal, Sudipta Shambhavi, Sakshi Patel, Ketan D Pramanik, Surabhi Dubey, Noopur Narasimhan, Subhash Madduri, Murali Krishna Pal, Biswajit Gokhale, Rajesh S Sankaranarayanan, Rajan |
author_sort | Patil, Gajanan S |
collection | PubMed |
description | Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4′-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and accept holo-ACP unlike other members of the ANL superfamily remains elusive. We show that FAALs have plugged the promiscuous canonical CoA-binding pockets and utilize highly selective alternative binding sites. These alternative pockets can distinguish adenosine 3′,5′-bisphosphate-containing CoA from holo-ACP and thus FAALs can distinguish between CoA and holo-ACP. These exclusive features helped identify the omnipresence of FAAL-like proteins and their emergence in plants, fungi, and animals with unconventional domain organizations. The universal distribution of FAALs suggests that they are parallelly evolved with FACLs for ensuring a CoA-independent activation and redirection of fatty acids towards lipidic metabolites. |
format | Online Article Text |
id | pubmed-8460268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-84602682021-09-24 A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation Patil, Gajanan S Kinatukara, Priyadarshan Mondal, Sudipta Shambhavi, Sakshi Patel, Ketan D Pramanik, Surabhi Dubey, Noopur Narasimhan, Subhash Madduri, Murali Krishna Pal, Biswajit Gokhale, Rajesh S Sankaranarayanan, Rajan eLife Biochemistry and Chemical Biology Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4′-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and accept holo-ACP unlike other members of the ANL superfamily remains elusive. We show that FAALs have plugged the promiscuous canonical CoA-binding pockets and utilize highly selective alternative binding sites. These alternative pockets can distinguish adenosine 3′,5′-bisphosphate-containing CoA from holo-ACP and thus FAALs can distinguish between CoA and holo-ACP. These exclusive features helped identify the omnipresence of FAAL-like proteins and their emergence in plants, fungi, and animals with unconventional domain organizations. The universal distribution of FAALs suggests that they are parallelly evolved with FACLs for ensuring a CoA-independent activation and redirection of fatty acids towards lipidic metabolites. eLife Sciences Publications, Ltd 2021-09-07 /pmc/articles/PMC8460268/ /pubmed/34490847 http://dx.doi.org/10.7554/eLife.70067 Text en © 2021, Patil et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Patil, Gajanan S Kinatukara, Priyadarshan Mondal, Sudipta Shambhavi, Sakshi Patel, Ketan D Pramanik, Surabhi Dubey, Noopur Narasimhan, Subhash Madduri, Murali Krishna Pal, Biswajit Gokhale, Rajesh S Sankaranarayanan, Rajan A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation |
title | A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation |
title_full | A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation |
title_fullStr | A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation |
title_full_unstemmed | A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation |
title_short | A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation |
title_sort | universal pocket in fatty acyl-amp ligases ensures redirection of fatty acid pool away from coenzyme a-based activation |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460268/ https://www.ncbi.nlm.nih.gov/pubmed/34490847 http://dx.doi.org/10.7554/eLife.70067 |
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