Synthesis of Amines for Active Pharmaceutical Ingredients Using the Whole-Cell Factory Saccharomyces Cerevisae.

Abstract

Whole-cell biocatalysis offers a sustainable alternative to traditional chemical synthesis for producing pharmaceutically relevant, often chiral, amines and amino acids. Saccharomyces cerevisiae has emerged as a privileged microbial chassis due to its robustness, ease of genetic manipulation, and GRAS status. This concise review summarizes recent advances in metabolic and genetic engineering of S. cerevisiae for amine biocatalysis, focusing on strategies to overcome bottlenecks such as enzyme gene expression, cofactor regeneration, and precursor channeling. The first section covers state-of-the-art methods for engineered strain construction, including genomic editing, optimization of gene expression (copy number, promoters, terminators, codon usage), and metabolic engineering (pathway balancing, compartmentalization, cofactor supply, transport proteins, auxiliary enzymes, and enzyme targeting via signal peptides), all enhancing product yields and enabling complex amine synthesis. The central section critically discusses compound families accessible via engineered S. cerevisiae, including various amines, amino alcohols, and amino acids such as l-carnitine, ergothioneine, halogenated tryptamine, serotonin, psilocybin, spermidine, l-ornithine, and mycosporine derivatives. Bioproduction of complex alkaloids, such as tropine derivatives (hyoscyamine and scopolamine) and ergot alkaloids, is also reviewed. Finally, current challenges and future perspectives are outlined, highlighting the integration of systems and synthetic biology tools to establish S. cerevisiae as a scalable platform for industrial amine production.

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