ATS2

TgATS2 is an apicoplast-resident acyltransferase in Toxoplasma gondii that couples organellar lipid synthesis to parasite cell division (PMID:32187549). Within the apicoplast it produces (lyso)phosphatidic acid, and this lipid product is required for recruitment of the dynamin TgDrpC during cytokinesis; genetic disruption of TgATS2 abolishes TgDrpC recruitment and impairs cytokinesis (PMID:32187549). TgATS2 activity also sets the balance between endogenous and exogenous lipid sourcing: loss of TgATS2 shifts parasites away from apicoplast de novo synthesis toward scavenging lipids from the host cell (PMID:32187549). Beyond these findings, no further mechanistic detail — including enzymatic characterization, substrate specificity, or structural basis — has been characterized in the available corpus.

1. 2020 Medium

   It was unknown how apicoplast lipid metabolism is linked to the machinery of parasite division; disruption of TgATS2 showed that its (lyso)phosphatidic acid product is required to recruit the dynamin TgDrpC and drive cytokinesis, establishing a direct lipid-to-division link.

   Evidence Genetic disruption of TgATS2 with analysis of TgDrpC recruitment and cytokinesis phenotype in Toxoplasma gondii

   PMID:32187549

   Open questions at the time

   • Enzymatic activity and substrate specificity of TgATS2 not directly reconstituted
   • Mechanism by which (lyso)phosphatidic acid recruits TgDrpC not defined
   • Single lab; no reciprocal or structural validation
2. 2020 Medium

   It was unclear what governs the parasite's reliance on de novo versus host-derived lipids; disruption of TgATS2 shifted lipid acquisition toward host scavenging, establishing TgATS2 as a determinant of the endogenous/exogenous lipid balance.

   Evidence Genetic disruption of TgATS2 with metabolic lipid profiling and tracking of scavenging versus de novo synthesis in Toxoplasma gondii

   PMID:32187549

   Open questions at the time

   • Regulatory mechanism controlling the metabolic switch not defined
   • Whether the scavenging shift is direct or a compensatory response to lost synthesis not resolved

• The biochemical enzymology of TgATS2 (substrate specificity, catalytic mechanism, structural basis) and the molecular mechanism linking its lipid product to TgDrpC recruitment remain uncharacterized.
• No in vitro reconstitution of acyltransferase activity
• No structural model
• No direct demonstration of (lyso)phosphatidic acid binding by TgDrpC