3.4 Evolution of key enzymes in the β-carotene metabolic pathway
using mutagenesis tools
To explore the potential of our mutagenesis tools in different
evolutionary scenarios, such as enhancing the production of valuable
compounds, we utilized them in the evolution of the CrtE ,CrtI and CrtYB genes in the β-carotene biosynthetic
pathway. We selected the β-carotene-producing yeast strain as the
chassis strain and added reverse T7 promoter sequences to CrtE ,CrtI , and CrtYB gene expression cassettes (Fig. 5). After
the introduction of mutagenesis plasmids into the chassis strain and
induction, we found that there were a few colonies of the strains
exhibited different colors. We selected four colonies with distinct
color changes and sequenced the target loci. The data suggested that
diverse mutations occurred in the CrtE , CrtI , andCrtYB expression cassettes, including transition and transversion
mutations. We analyzed these base conversions and found that most of
them were C and G mutations, which was also consistent with the mutation
characteristics of our mutagenesis tools mentioned above.
We then respectively introduced these single point mutations into the
original β-carotene-producing strain and verified whether these strains
could still show different colors. We observed that even without the
mutagenic fusion proteins, the strains with point mutations still
exhibited obvious color changes, indicating that these mutations can
effectively alter colony colors and β-carotene yields.
We proved that our mutagenesis tools can generate random mutations in
the key enzymes in the β-carotene biosynthetic pathway, resulting in
increased β-carotene yields. These results demonstrated that our
mutagenesis tools can be applied to the evolution of non-growth-limiting
genes. Even in the absence of the growth pressure or selection, the
mutagenesis fusion proteins were able to function robustly.