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Eun Joong Oh

Publications and source records attributed to Eun Joong Oh.

2 recordsLinked to original sources

Biological Parts in Yeast Synthetic Biology: From Regulatory Elements to Predictive Design Platforms.

Yeasts, particularly Saccharomyces cerevisiae, are important eukaryotic chassis for synthetic biology because of their tractable genetics, versatile toolkits, and broad utility in metabolic engineering and functional genomics. Progress in this field has been driven by biological parts that enable programmable control of gene expression and cellular behavior. Early efforts focused mainly on promoters, terminators, and other regulatory elements for tuning individual genes. However, as engineering expanded to multigene pathways, genetic circuits, and dynamic regulatory systems, the limits of part-centric design became clear. Part performance is often shaped by genomic context, chromatin state, host physiology, and interactions with other components, which restricts modularity and predictability. In response, yeast synthetic biology is shifting toward integrated design frameworks combining multilayer regulation, standardized assembly, automated experimentation, and computational modeling. This review provides an integrated perspective on the evolution of biological parts across DNA-, RNA-, and protein-level regulation, connecting these advances with assembly frameworks, biofoundries, and machine learning to trace the trajectory from part-centric engineering toward predictive, system-level design in yeast synthetic biology.

Biofoundry

Metabolic Engineering of Probiotic Saccharomyces boulardii Enables Intestinal 3-Hydroxybutyrate Delivery and Alters Short-Chain Fatty Acid Profiles in Mice.

3-Hydroxybutyric acid (3-HB) is a bioactive ketone body involved in the regulation of intestinal inflammation and metabolic homeostasis. Although engineered bacterial probiotics have been developed for localized 3-HB delivery, their susceptibility to antibacterial antibiotics may limit their use during concurrent antibiotic treatment. The probiotic yeast Saccharomyces boulardii offers an alternative host for intestinal 3-HB delivery because of its compatibility with antibacterial antibiotics and the availability of well-established genetic engineering tools. Here, we engineered S. boulardii for 3-HB production using Cas9-mediated genome editing. A heterologous 3-HB biosynthetic pathway was introduced into S. boulardii MYA-797, and endogenous acetyl-CoA and ethanol metabolism was subsequently rewired by overexpressing ACS1, deleting ADH1, and overexpressing ADH7. The optimized strain, SbDY02, produced 1.7 g/L 3-HB under microaerobic conditions. Oral administration of SbDY02 to C57BL/6J mice increased fecal 3-HB and short-chain fatty acid (SCFA) concentrations by 1.89-fold and 1.68-fold, respectively, compared with mice receiving the parental strain. Repeated administration also increased fecal acetate and circulating total SCFAs, butyrate, and propionate. In human colonic epithelial cells, purified 3-HB attenuated lipopolysaccharide-induced p38 MAPK phosphorylation, supporting its direct activity toward inflammation-associated epithelial signaling. To our knowledge, this study provides the first demonstration of a 3-HB-producing probiotic yeast and links central metabolic engineering of S. boulardii with increased 3-HB availability, altered SCFA profiles, and a host-relevant epithelial response.

3-hydroxybutyrate