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Last update 08 May 2025

IPC synthase

Last update 08 May 2025

Basic Info

Synonyms

AUR1, Aureobasidin A resistance protein homolog, Inositol phosphorylceramide synthase

+ [1]

Introduction

Catalyzes the addition of a phosphorylinositol group onto ceramide to form inositol phosphorylceramide, an essential step in sphingolipid biosynthesis.

Drugs associated with IPC synthase

Aureobasidin A-based cyclic peptides(AureoGen, Inc.)

Target

IPC synthase

Mechanism

IPC synthase inhibitors

Active Org.

Merck Sharp & Dohme Corp. [+1]

Originator Org.

AureoGen, Inc.

Active Indication

Mycoses

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Basifungin

Target

IPC synthase

Mechanism

IPC synthase inhibitors

Active Org.-

Originator Org.

Nippon Kayaku Co., Ltd.

Active Indication-

Inactive Indication

Mycoses

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IPC synthase

100 Translational Medicine associated with IPC synthase

0 Patents (Medical) associated with IPC synthase

124

Literatures (Medical) associated with IPC synthase

05 Feb 2025·mBio

Stage-specific function of sphingolipid synthases in African trypanosomes

Article

Author: Koeller, Carolina M. ; Sharif, Mohamed ; Heise, Norton ; Bangs, James D.

ABSTRACT The protozoan parasite Trypanosoma brucei is the only known eukaryote capable of synthesizing the three main phosphosphingolipids: sphingomyelin (SM), inositol phosphorylceramide (IPC), and ethanolamine phosphorylceramide (EPC). It has four paralogous genes encoding sphingolipid synthases ( TbSLS1–4 ). TbSLS1 is a dedicated IPC synthase, TbSLS2 is a dedicated EPC synthase, and TbSLS3 and TbSLS4 are bifunctional SM/EPC synthases. IPC synthesis occurs exclusively in the procyclic insect stage (PCF), EPC is limited to the mammalian bloodstream form (BSF), and SM is synthesized throughout the life cycle. TbSLSs are indispensable for the viability of BSF and are, thus, potential drug targets. The relative stage-specific expression of each TbSLS paralog was compared, and the results match phosphosphingolipid content. Induction of pan-specific RNAi silencing was lethal in both BSF and PCF. To investigate individual TbSLS functions, separate HA-tagged genes, recoded to be RNAi-resistant (RNAi R ), were engineered to replace a single allele of the entire TbSLS locus within parental BSF and PCF RNAi cell lines. RNAi RTbSLS3 and TbSLS4 both rescued BSF growth under silencing. Expression of RNAi RTbSLS1 , normally repressed in BSF, did not rescue BSF viability but was not detrimental to normal in vitro growth. RNAi RTbSLS1 , TbSLS3 , and TbSLS4 were each sufficient to rescue PCF growth, indicating IPC is not essential for PCF viability in vitro . All TbSLSs localize to distal Golgi compartments in both BSF and PCF cells. These findings raise interesting questions about the roles of individual phosphosphingolipids in in vivo infection of the mammalian and tsetse hosts. IMPORTANCEAfrican trypanosomes are eukaryotic pathogens that cause human and veterinary African trypanosomaisis. Uniquely, they synthesize all three major phosphosphingolipid species using four distinct sphingolipid synthases (SLS). This work details the function of each SLS in both bloodstream and insect form parasites. Novel and unexpected sphingolipid dependences are found in each stage. These results are consistent with this metabolic pathway being a valid target for chemotherapeutic intervention.

01 Dec 2024·Molecular and Biochemical Parasitology

Diversification of sphingolipid synthase activities in kinetoplastid protozoa

Article

Author: Bangs, James D ; Bangs, James D. ; Jackson, Andrew P ; Jackson, Andrew P. ; Ciganda, Martin

Phosphosphingolipids (PSL) are essential components of eukaryotic membranes. The major PSL in fungi and protists is inositol phosphorylceramide (IPC), while sphingomyelin (SM), and to a lesser extent ethanolamine phosphorylceramide (EPC) predominate in mammals. Most kinetoplastid protozoa have a syntenic locus that encodes a single sphingolipid synthase (SLS) gene. Uniquely, among the kinetoplastids, the salivarian (African) trypanosomes have expanded this locus from a single gene in Trypanosoma vivax (TvSLS) to four genes in T. brucei (TbSLS1-4). We have previously shown that one of these is an IPC synthase, while the others are SM/EPC synthases, and that specificity is controlled by a single signature residue (IPC, serine; SM/EPC, phenylalanine). This residue is serine in T. cruzi and Leishmania major SLSs, both of which are demonstrated IPC synthases. However, T. vivax has a tyrosine at this residue raising the issue of specificity. Using a liposome-supplemented in vitro translation system we now show that T. vivax SLS is an SM/EPC synthase, and that the basal kinetoplastid Bodo saltans SLS is an IPC synthase (serine). We use these data, and a multiple alignment of available sequences, to discuss the evolution of kinetoplastid SLSs and their unique expansion in T. brucei and related salivarian trypanosomes.

01 Sep 2024·iScience

Complex sphingolipid profiling and identification of an inositol-phosphorylceramide synthase in Dictyostelium discoideum

Article

Author: Holthuis, Joost C M ; Barisch, Caroline ; Eising, Sebastian ; Listian, Stevanus A. ; Fröhlich, Florian ; Holthuis, Joost C.M. ; Walter, Stefan ; Mazur, Anna-Carina ; Ufelmann, Edwin ; Listian, Stevanus A ; Kol, Matthijs

Dictyostelium discoideum is a professional phagocyte frequently used to study cellular processes underlying the recognition, engulfment, and infection course of microbial pathogens. Sphingolipids are abundant components of the plasma membrane that bind cholesterol, control membrane properties, participate in signal transmission, and serve as adhesion molecules in recognition processes relevant to immunity and infection. By combining lipidomics with a bioinformatics-based cloning strategy, we show here that D. discoideum produces phosphoinositol-containing sphingolipids with predominantly phytoceramide backbones. Cell-free expression of candidate inositol-phosphorylceramide (IPC) synthases from D. discoideum enabled identification of an enzyme that selectively catalyzes the transfer of phosphoinositol from phosphatidylinositol onto ceramide. The IPC synthase, DdIPCS1, shares multiple sequence motifs with yeast IPC and human sphingomyelin synthases and localizes to the Golgi apparatus as well as the contractile vacuole of D. discoideum. These findings open up important opportunities for exploring a role of sphingolipids in phagocytosis and infection across major evolutionary boundaries.

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IPC synthase

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