CDS2

TgCDS2 is a prokaryotic-type CDP-diacylglycerol synthase that localizes to the apicoplast of Toxoplasma gondii, functioning in parallel with the eukaryotic-type, ER-resident TgCDS1 to sustain phospholipid biogenesis (PMID:28314772). The apicoplast-derived CDP-DAG pool it produces is channeled preferentially toward phosphatidylglycerol synthesis, as deletion of TgCDS2 specifically depletes phosphatidylglycerol (PMID:28314772). The two isoforms are functionally cooperative and collectively essential: deleting TgCDS2 in a TgCDS1-knockdown background abolishes the residual parasite growth, establishing that combined CDP-DAG production supports parasite replication (PMID:28314772). Beyond these compartmentalized activities and their genetic interaction, no further mechanistic detail on TgCDS2 has been characterized in the available corpus.

1. 2017 Medium

   Establishing that T. gondii encodes two distinct CDP-diacylglycerol synthases resolved where CDP-DAG is generated in the parasite, revealing an apicoplast-localized prokaryotic-type enzyme separate from the ER-resident eukaryotic-type isoform.

   Evidence Subcellular fractionation and localization distinguishing TgCDS2 (apicoplast) from TgCDS1 (ER)

   PMID:28314772

   Open questions at the time

   • Direct enzymatic characterization of TgCDS2 CDP-DAG synthase activity not shown
   • No structural model of the enzyme
2. 2017 Medium

   Linking TgCDS2 to a specific lipid output answered what the apicoplast CDP-DAG pool is used for, showing it feeds phosphatidylglycerol synthesis in the mitochondria.

   Evidence Conditional gene deletion combined with lipidomic analysis showing specific reduction of phosphatidylglycerol

   PMID:28314772

   Open questions at the time

   • Mechanism of CDP-DAG transfer from apicoplast to mitochondria not defined
   • Enzymes downstream converting CDP-DAG to phosphatidylglycerol not identified in this study
3. 2017 Medium

   Genetic epistasis clarified whether the two CDS isoforms are redundant or cooperative, demonstrating they are jointly essential for parasite survival.

   Evidence Consecutive conditional knockdown of TgCDS1 with deletion of TgCDS2 and parasite growth assays

   PMID:28314772

   Open questions at the time

   • Extent of functional overlap versus division of labor between the two enzymes not fully resolved
   • Whether TgCDS2 loss alone impairs replication under standard conditions not stated

• The biochemical activity, structure, and regulation of TgCDS2, and the trafficking route coupling apicoplast CDP-DAG to mitochondrial phosphatidylglycerol synthesis, remain uncharacterized.
• No in vitro reconstitution of TgCDS2 enzymatic activity
• No structural information
• Interorganelle lipid transport mechanism unknown