ArticleNucleic acids research2020
Phylogenetic debugging of a complete human biosynthetic pathway transplanted into yeast.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 24 citations in OpenAlex.
- The synthetic future of algal genomes.Cell genomics · 2024Review
- Humanization reveals pervasive incompatibility of yeast and human kinetochore components.G3 (Bethesda, Md.) · 2023Article
- Rapid, scalable, combinatorial genome engineering by marker-less enrichment and recombination of genetically engineered loci in yeast.Cell reports methods · 2023Article
- Humanized yeast to model human biology, disease and evolution.Disease models & mechanisms · 2022Review
- Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants.Genes · 2021Review
- A supernumerary designer chromosome for modular in vivo pathway assembly in Saccharomyces cerevisiae.Nucleic acids research · 2021Article
- Engineered dual selection for directed evolution of SpCas9 PAM specificity.Nature communications · 2021Article
- Cross-Species Complementation of Nonessential Yeast Genes Establishes Platforms for Testing Inhibitors of Human Proteins.Genetics · 2020Article
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Authors and funding
12 authors at 4 institutions in 1 country.
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Abstract
Cross-species pathway transplantation enables insight into a biological process not possible through traditional approaches. We replaced the enzymes catalyzing the entire Saccharomyces cerevisiae adenine de novo biosynthesis pathway with the human pathway. While the 'humanized' yeast grew in the absence of adenine, it did so poorly. Dissection of the phenotype revealed that PPAT, the human ortholog of ADE4, showed only partial function whereas all other genes complemented fully. Suppressor analysis revealed other pathways that play a role in adenine de-novo pathway regulation. Phylogenetic analysis pointed to adaptations of enzyme regulation to endogenous metabolite level 'setpoints' in diverse organisms. Using DNA shuffling, we isolated specific amino acids combinations that stabilize the human protein in yeast. Thus, using adenine de novo biosynthesis as a proof of concept, we suggest that the engineering methods used in this study as well as the debugging strategies can be utilized to transplant metabolic pathway from any origin into yeast.
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