Gangliosides are attractive commercial targets for biomedical research, diagnostics, and therapeutics due to their critical roles in pathogen infection, cell-cell communication, and inflammation. Neuroprotective and neurorestorative functions of gangliosides have been explored for treating Parkinson’s disease and other neurological indications such as traumatic brain injury. Isolation of specific gangliosides from animal brains cannot sustainably meet therapeutic demand and raises risks of zoonotic contamination. Chemoenzymatic synthesis is an efficient alternative that minimizes protection and deprotection steps and avoids undesired regio- and stereoisomers. IMCS is commercializing kits that enable facile and affordable enzymatic synthesis of custom gangliosides from a synthetic lactosylsphingosine acceptor. Here we present our first two One-Pot MultiEnzyme (OPME) kits, which enable synthesis of GM3 and GD3 gangliosides. Each kit contains an inorganic pyrophosphatase, CMP-sialic acid synthetase, and one of two sialyltransferases, which were prepared at multi-gram scale via fed-batch fermentation, immobilized metal affinity chromatography, and size-exclusion chromatography. Liquid storage formulation and reaction optimization resulted in robust OPME systems that rapidly produce Neu5Aca2,3-lactosylsphinogosine (GM3Sph) and Neu5Aca2,8-Neu5Aca2,3-lactosylsphinogosine (GD3Sph). Additional OPME kits that enable synthesis of GM2, GM1, and other gangliosides are in development. These OPME kits will allow the broader scientific community to access custom gangliosides to better understand their biological roles.

One-pot multienzyme (OPME) sialylation kits for custom ganglioside synthesis

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