Authors: Etienne Deragon, Martin Schuler, Riccardo Aiese Cigliano, Younès Dellero, Gregory Si Larbi, Denis Falconet, Juliette Jouhet, Eric Maréchal, Morgane Michaud, Alberto Amato, Fabrice Rébeillé.

Institutions:

  • Laboratoire de Physiologie Cellulaire et Végétale, Université Grenoble Alpes, CNRS, CEA, INRAE, CEDEX 9, 38054 Grenoble, France
  • Sequentia Biotech SL, Carrer Pamplona, 08018 Barcelona, Spain
  • Institute of Genetic, Environment and Plant Protection, UMR 1349 IGEPP INRA, Agrocampus Ouest Rennes, Université Rennes 1, Domaine de la Motte BP35327, CEDEX, 35653 Le Rheu, France

Publication: Cells

Date: September 2021

Full paper: An Oil Hyper-Accumulator Mutant Highlights Peroxisomal ATP Import as a Regulatory Step for Fatty Acid Metabolism in Aurantiochytrium limacinum

Abstract:

Thraustochytrids are marine protists that naturally accumulate triacylglycerol with long chains of polyunsaturated fatty acids, such as ω3-docosahexaenoic acid (DHA). They represent a sustainable response to the increasing demand for these “essential” fatty acids (FAs). Following an attempt to transform a strain of Aurantiochytrium limacinum, we serendipitously isolated a clone that did not incorporate any recombinant DNA but contained two to three times more DHA than the original strain. Metabolic analyses indicated a deficit in FA catabolism. However, whole transcriptome analysis did not show down-regulation of genes involved in FA catabolism. Genome sequencing revealed extensive DNA deletion in one allele encoding a putative peroxisomal adenylate transporter. Phylogenetic analyses and yeast complementation experiments confirmed the gene as a peroxisomal adenylate nucleotide transporter (AlANT1), homologous to yeast ScANT1 and plant peroxisomal adenylate nucleotide carrier AtPNC genes. In yeast and plants, a deletion of the peroxisomal adenylate transporter inhibits FA breakdown and induces FA accumulation, a phenotype similar to that described here. In response to this metabolic event, several compensatory mechanisms were observed. In particular, genes involved in FA biosynthesis were upregulated, also contributing to the high FA accumulation. These results support AlANT1 as a promising target for enhancing DHA production in Thraustochytrids.