Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: A yeast with muscle does not run faster: full humanization of the glycolytic pathway in Saccharomyces cerevisiae While transplantation of single genes in yeast plays a key role in elucidating gene functionality in metazoans, technical challenges hamper the humanization of full pathways and processes. Empowered by advances in synthetic biology, this study demonstrates the feasibility and implementation of full humanization of glycolysis in yeast. Single gene and full pathway transplantation revealed the remarkable conservation of both glycolytic and moonlighting functions and, combined with evolutionary strategies, brought to light novel, context-dependent responses. Remarkably, human hexokinase 1 and 2, but not 4, required mutations in their catalytic or allosteric sites for functionality in yeast, while hexokinase 3 was unable to complement its yeast ortholog. Comparison with human tissues cultures showed the preservation of turnover numbers of human glycolytic enzymes in yeast and human cell cultures. This demonstration of transplantation of an entire, essential pathway paves the way to the establishment of species, tissue and disease-specific metazoan models.

One Sentence SummaryThis work demonstrates the successful humanization of an entire pathway in Saccharomyces cerevisiae and establishes an attractive strategy to study (human) glycolysis architecture and regulation.

HighlightsO_LIThe successful humanization of the entire glycolytic pathway in yeast offers new microbial models for both fundamental and applied studies.
C_LIO_LIBoth glycolytic and moonlighting functions and turnover numbers of glycolytic enzymes are highly conserved between yeast and human.
C_LIO_LIFunctionality of human hexokinases 1 and 2 in yeast requires mutations in the catalytic or allosteric binding sites.
C_LIO_LICombination of single gene and full transplantation with laboratory evolution reveals context-dependent activity and evolution of glycolytic enzymes.
C_LI
21
The categories of this paper are: toxicology
26
The categories of this paper are: biochemistry
4
The categories of this paper are: neuroscience
15
The categories of this paper are: developmental
10
The categories of this paper are: and
29
The categories of this paper are: education
12
The categories of this paper are: behavior
13
The categories of this paper are: animal
31
The categories of this paper are: paleontology
25
The categories of this paper are: bioengineering
24
The categories of this paper are: cancer
27
The categories of this paper are: pathology
17
The categories of this paper are: molecular
30
The categories of this paper are: scientific
20
The categories of this paper are: pharmacology
28
The categories of this paper are: communication