Transcriptomic analysis of engineered and improved Pichia pastoris for S-adenosyl-l-methionine (SAM) production

SAM is the principal methyl group donor in all living organisms, and has attracted much interest in clinical research. We improved SAM production in engineered P. pastoris strain GS115/DS56 by overexpression of the recombinant methionine adenosyltransferase (MAT) gene DS56, and further enhanced SAM prduction in G12-CBS by downregulation of the cystathionine β-synthase (CBS) gene CYS4 with a weak promoter G12. We performed the pairwise transcriptome comparisons between high-producing (HP) and low-producing (LP) strains, in order to understand the impact of SAM accumulation on the P. pastoris physiology and to identify genome-wide targets for further improving SAM production.