Exploring Conventional and Nonconventional Yeasts for Producing Bioplastic and Pharmaceutical Precursors Via Shikimate Pathway

Shikimate pathway serves an essential metabolic role in all living organisms.  Not only are the three aromatic amino acids synthesized through this pathway, but also many bioactive alkaloid and flavonoid types of secondary metabolites are derived from here.  In addition to the ability to express membrane-bound cytochrome P450 enzymes, yeast is generally recognized as safe (GRAS) for producing compounds used as nutraceutical and pharmaceutical ingredients.  On the other hand, the synthesis of muconic acid, the precursor of nylon 6,6 and polyethylene terephthalate (PET), was also established recently in yeast as a branch-out pathway from shikimate biosynthesis to replace the environmentally harmful petrochemical synthetic processes.  However, the intrinsically complicated genetic and metabolic regulations involved in yeast central carbon metabolism prohibit the production of high-value compounds derived from this treasure at levels of commercial interest.

Here we report our recent progress on establishing yeast platforms to produce shikimate and shikimate-derived bioplastic and pharmaceutical precursors through three aspects: (1) developing a seamless integration with electrochemical hydrogenation at ambient temperature and pressure, which allows the creation of a novel nylon 6,6 replacement polymer with tunable properties¹; (2) deciphering the bottlenecks of shikimate biosynthesis in both conventional and nonconventional yeast species and achieving the highest production among all the compounds derived from this pathway using yeast platforms^2,3; (3) establishing platform technologies to enable rapid functional modifications of a series of high-potential nonconventional yeast species⁴.  Our work represents the new explorations in expanding the current collection of microbial factories and bridging the gap between biological and chemical catalysis to nurture a sustainable biorenewable chemical industry.

References:

1. M. Suastegui, J. E. Matthiesen, J. M. Carraher, N. Hernandez, N. R. Quiroz, A. Okerlund, E. W. Cochran, Z. Shao, and J.-P. Tessonnier, “Combining Metabolic Engineering and Electrocatalysis: Application to the Production of Polyamides from Sugar”, Angewandte Chemie International Edition DOI: 10.1002/anie.201509653 (featured as the front cover, 2016).

2. M. Suastegui, W. Guo, X. Feng, and Z. Shao, “Investigating Strain Dependency in the Production of Aromatic Compounds in Saccharomyces cerevisiae” (submitted, 2016).

3. M. Gao, M. Cao, M. Suastegui, Y. Wu, J. Shanks, and Z. Shao, “Innovating a Nonconventional Yeast Platform for Producing Shikimate as the Building Block of High-Value Aromatics” (submitted, 2016).

4. M. Cao, M. Gao, C. Lopez, Y. Wu, A. Seetharam, A. Severin, and Z. Shao. “Rapid Isolation of the Hubs of Chromosomes to Facilitate Nonconventional Yeast Engineering” (submitted, 2016).