Multi-omics profiling finds synbio milk differs nutritionally from bovine milk and contains 93 uncharacterized fungal metabolites and 236 fungal proteins.

Synbio milk, containing recombinant bovine β-lactoglobulin (β-LG), produced in the fungus Trichoderma reesei, was deficient nutritionally compared to bovine milk. It also contained both fungal proteins and fungal metabolites never verified safe for human consumption. By three independent methods synbio milk was found to contain predominantly fungal protein, not the 90–99% β-LG, claimed by the product developer. By (1) shotgun proteomics, (2) ELISA and classical protein analysis, and (3) simulated mixing experiments, measuring percent deviation of the amino acid composition of synbio milk from that of bovine milk, fungal protein content was found to be 75.1%, 86.5% and 90–95%, respectively. Additionally, high sensitivity untargeted mass spectrometry revealed substantial levels of 69 nutrients in bovine milk, of which only 7 were present in small amounts in synbio milk. This analysis also revealed 93 compounds in synbio milk, byproducts/waste products of fungal fermentation, whose chemical identities could not be established searching large mass spectral databases, suggesting they are novel compounds. Neither these nor the fungal proteins found in the synbio milk have been tested for safety or allergenicity at exposure levels relevant for synbio milk consumption. Therefore, comprehensive toxicity and allergenicity testing are needed to assess the safety of synbio milk for human consumption.