Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria

Abstract Phosphatidic acid phosphatase (PAP) catalyzes the dephosphorylation of phosphatidic acid (PA) yielding diacylglycerol (DAG), the lipid precursor for triacylglycerol (TAG) biosynthesis. PAP activity has a key role in the regulation of PA flux towards TAG or glycerophospholipid synthesis. In...

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Autores principales:	Agostina Crotta Asis, Franco Savoretti, Matías Cabruja, Hugo Gramajo, Gabriela Gago
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b8bfeae638204e2d8407244da573c2c7
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spelling	oai:doaj.org-article:b8bfeae638204e2d8407244da573c2c72021-12-02T17:45:18ZCharacterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria10.1038/s41598-021-92721-y2045-2322https://doaj.org/article/b8bfeae638204e2d8407244da573c2c72021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92721-yhttps://doaj.org/toc/2045-2322Abstract Phosphatidic acid phosphatase (PAP) catalyzes the dephosphorylation of phosphatidic acid (PA) yielding diacylglycerol (DAG), the lipid precursor for triacylglycerol (TAG) biosynthesis. PAP activity has a key role in the regulation of PA flux towards TAG or glycerophospholipid synthesis. In this work we have characterized two Mycobacterium smegmatis genes encoding for functional PAP proteins. Disruption of both genes provoked a sharp reduction in de novo TAG biosynthesis in early growth phase cultures under stress conditions. In vivo labeling experiments demonstrated that TAG biosynthesis was restored in the ∆PAP mutant when bacteria reached exponential growth phase, with a concomitant reduction of phospholipid synthesis. In addition, comparative lipidomic analysis showed that the ∆PAP strain had increased levels of odd chain fatty acids esterified into TAGs, suggesting that the absence of PAP activity triggered other rearrangements of lipid metabolism, like phospholipid recycling, in order to maintain the wild type levels of TAG. Finally, the lipid changes observed in the ∆PAP mutant led to defective biofilm formation. Understanding the interaction between TAG synthesis and the lipid composition of mycobacterial cell envelope is a key step to better understand how lipid homeostasis is regulated during Mycobacterium tuberculosis infection.Agostina Crotta AsisFranco SavorettiMatías CabrujaHugo GramajoGabriela GagoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agostina Crotta Asis Franco Savoretti Matías Cabruja Hugo Gramajo Gabriela Gago Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria
description	Abstract Phosphatidic acid phosphatase (PAP) catalyzes the dephosphorylation of phosphatidic acid (PA) yielding diacylglycerol (DAG), the lipid precursor for triacylglycerol (TAG) biosynthesis. PAP activity has a key role in the regulation of PA flux towards TAG or glycerophospholipid synthesis. In this work we have characterized two Mycobacterium smegmatis genes encoding for functional PAP proteins. Disruption of both genes provoked a sharp reduction in de novo TAG biosynthesis in early growth phase cultures under stress conditions. In vivo labeling experiments demonstrated that TAG biosynthesis was restored in the ∆PAP mutant when bacteria reached exponential growth phase, with a concomitant reduction of phospholipid synthesis. In addition, comparative lipidomic analysis showed that the ∆PAP strain had increased levels of odd chain fatty acids esterified into TAGs, suggesting that the absence of PAP activity triggered other rearrangements of lipid metabolism, like phospholipid recycling, in order to maintain the wild type levels of TAG. Finally, the lipid changes observed in the ∆PAP mutant led to defective biofilm formation. Understanding the interaction between TAG synthesis and the lipid composition of mycobacterial cell envelope is a key step to better understand how lipid homeostasis is regulated during Mycobacterium tuberculosis infection.
format	article
author	Agostina Crotta Asis Franco Savoretti Matías Cabruja Hugo Gramajo Gabriela Gago
author_facet	Agostina Crotta Asis Franco Savoretti Matías Cabruja Hugo Gramajo Gabriela Gago
author_sort	Agostina Crotta Asis
title	Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria
title_short	Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria
title_full	Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria
title_fullStr	Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria
title_full_unstemmed	Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria
title_sort	characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b8bfeae638204e2d8407244da573c2c7
work_keys_str_mv	AT agostinacrottaasis characterizationofkeyenzymesinvolvedintriacylglycerolbiosynthesisinmycobacteria AT francosavoretti characterizationofkeyenzymesinvolvedintriacylglycerolbiosynthesisinmycobacteria AT matiascabruja characterizationofkeyenzymesinvolvedintriacylglycerolbiosynthesisinmycobacteria AT hugogramajo characterizationofkeyenzymesinvolvedintriacylglycerolbiosynthesisinmycobacteria AT gabrielagago characterizationofkeyenzymesinvolvedintriacylglycerolbiosynthesisinmycobacteria
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Characterization of key enzymes involved in triacylglycerol biosynthesis in mycobacteria

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