The first biohybrids (biological-inorganic hybrid systems) focused mainly on the fixation of atmospheric carbon dioxide and the production of alternative energies. While these were promising, there were challenges. For instance, semiconductors, which contain toxic metals, are assembled directly on bacterial cells and often harm them in the process. In addition, the initial focus on carbon-fixing microbes has limited the range of products to relatively simple molecules. A team from the Wyss Institute for Biologically Inspired Engineering at Harvard reported on a solution to these problems.
Core faculty member Neel Joshi explained, “While our strategy conceptually builds on earlier bacterial biohybrid systems that were engineered by our collaborator Daniel Nocera and others, we expanded the concept to yeast—an organism that is already an industrial workhorse and is genetically easy to manipulate—with a modular semiconductor component that provides biochemical energy to yeast’s metabolic machinery without being toxic.” As a result of the combined manipulations, yeasts’ ability to produce shikimic acid, an important precursor of the anti-viral drug Tamiflu, several other medicines, nutraceuticals, and fine chemicals, was significantly enhanced.
Saccharomyces cerevisiae naturally produces shikimic acid to generate some of its building blocks for the synthesis of proteins and other biomolecules. However, by genetically modifying the yeast’s central metabolism, the researchers enabled the cells to funnel more of the carbon atoms that their main nutrient source, the sugar glucose, contains into the pathway that produces shikimic acid and prevent the loss of carbon to alternative pathways by disrupting one of them.
“This scalable approach creates an entirely new design space for future biohybrid technologies, said postdoctoral fellow Junling Guo. “In future efforts, the nature of semiconductors and the type of genetically engineered yeast cells can be varied in a plug-and-play fashion to expand the type of manufacturing processes and range of bioproducts.”