Genetically engineered microbes such as bacteria and yeasts have long been used as living factories to produce drugs and fine chemicals. More recently, researchers have started to combine bacteria with semiconductor technology that, similar to solar panels on a roof, harvests energy from light and, when coupled to the microbes’ surface, boosts their biosynthetic potential.
The first “biological-inorganic hybrid systems,” or biohybrids, largely focused on fixing atmospheric carbon dioxide and producing alternative energies. While they were promising, they also revealed key challenges. For example, semiconductors, which are made from toxic metals, to date have been assembled directly on bacterial cells, which they often damage in the process. In addition, the focus on carbon-fixing microbes has limited the range of products to relatively simple molecules. If biohybrids could be created based on microorganisms equipped with more complex metabolisms, it would open new paths for production of a much wider range of chemicals useful for many applications.
Now, in a study in the journal Science, a multidisciplinary team led by Professor Neel Joshi and postdoctoral fellows Junling Guo and Miguel Suástegui of Harvard’s Wyss Institute for Biologically Inspired Engineering and the John A. Paulson School of Engineering and Applied Sciences (SEAS) presents a highly adaptable solution to these challenges.
“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,” said Joshi, who is a core faculty member at the Wyss Institute and associate professor at SEAS. Co-author Nocera is the Patterson Rockwood Professor of Energy at Harvard University.
As a result of these manipulations, yeasts’ ability to produce shikimic acid, an important precursor of the antiviral drug Tamiflu, several other medicines, nutraceuticals, and fine chemicals, was significantly enhanced.