Predicting complex phenotype–genotype interactions to enable yeast engineering: Saccharomyces cerevisiae as a model organism and a cell factory

Abstract

There is an increasing use of systems biology approaches in both “red” and “white” biotechnology in order to enable medical, medicinal, and industrial applications. The intricate links between genotype and phenotype may be explained through the use of the tools developed in systems biology, synthetic biology, and evolutionary engineering. Biomedical and biotechnological research are among the fields that could benefit most from the elucidation of this complex relationship. Researchers have studied fitness extensively to explain the phenotypic impacts of genetic variations. This elaborate network of dependencies and relationships so revealed are further complicated by the influence of environmental effects that present major challenges to our achieving an understanding of the cellular mechanisms leading to healthy or diseased phenotypes or optimized production yields. An improved comprehension of complex genotype–phenotype interactions and their accurate prediction should enable us to more effectively engineer yeast as a cell factory and to use it as a living model of human or pathogen cells in intelligent screens for new drugs. This review presents different methods and approaches undertaken toward improving our understanding and prediction of the growth phenotype of the yeast Saccharomyces cerevisiae as both a model and a production organism.

Yeast diversity and native vigor for flavor phenotypes

“…Because flavor traits are not necessarily essential for energy-yielding metabolism or cell survival, we can speculate that underlying genetic pathways are less affected by the positive selection pressures that contribute to increased whole-genome variability during microbial evolution [47,50]. In the same way, dynamic interactions between cells and fermentation media and microbial competition during food processes increase the complexity of the system, resulting in hard-to-predict phenotypegenotype interactions [50].…”

“…In the same way, dynamic interactions between cells and fermentation media and microbial competition during food processes increase the complexity of the system, resulting in hard-to-predict phenotypegenotype interactions [50]. Furthermore, compounds that are normally considered to be plant metabolites, such as resveratrol or monoterpenes, can also be produced by endophytic fungi during growth within the plant [51,52], as well as during yeast grape-must fermentation from sugars [53].…”

A new strategy for seamless gene editing and marker recycling in Saccharomyces cerevisiae using lethal effect of Cwp1

“…The budding yeast Saccharomyces cerevisiae is an attractive model organism for fundamental biological research and powerful cell factory for industrial application (Dikicioglu, Pir, & Oliver, 2014;Hong & Nielsen, 2012). Complex and multiple genomic engineering in S. cerevisiae therefore turns commonplace.…”

High molecular weight DNA assembly in vivo for synthetic biology applications

“…The Gramnegative bacterium Escherichia coli, the Gram-positive bacterium Bacillus subtilis and yeast Saccharomyces cerevisiae are the most frequently used synthetic biology ''workhorses'' and hosts for DNA assembly in vivo. [20][21][22][23][24][25] A number of genomes have been assembled to date, including the entire 583 kb, 1.08 Mb, and 3.5 Mb genomes of Mycoplasma genitalium, Mycoplasma mycoides [26,27] and Synechocystis PCC6803 [28], respectively. The M. mycoides genome assembly led to the construction of the first cell (dubbed ''Synthia''), controlled solely by a chemically synthesized genome.…”