An immense number of chemicals and enzymes are currently produced at industrial scales using biological production processes. Citric acid? Millions of tons are produced each year by Aspergillus strains. Rennet for your cheese? That’s most likely from E. parasitica fermentation. Cellulose for that stone-washed jeans look? T. reesei. Biological production is a vast, multi-billion dollar industry.Despite this, there is a certain simplicity to bio-production. The majority of molecules are made by screening tens of thousands of micro-organism strains, identifying the best producers, and then attempting to improve the yield. Essentially this is optimisation at a grand scale, with the smallest increase in yield percentage adding up to vast profits.But what about the other approach? In a world in which microbial genetic manipulation is commonplace, is it possible to design the cellular factory to our own specifications, so that it produces our favorite chemical with minimal complications? The answer is yes, but it took years of research and development to get to this point.

At the vanguard of this work is Amyris Inc., which was founded in 2003 by members of the University of California, Berkeley. These scientists, including our two speakers at SynBioBeta SF, Jay Keasling and Kinkead Reiling, took the then-nascent science of biosynthesis into their hands and ran with it.

Anti-malarials for the masses

To understand this we need to take a step back, and look at malaria. Malaria is a scourge of developing countries, particularly within Africa, killing hundreds of thousands every year. The best treatment consists of a combination of drugs which include artemisinin, a strong antimalarial purified from the leaves of the Artemisia annua tree. Given this natural source, artemisinin is thus expensive to produce and subject to large supply and price fluctuations.

This is where the work of our two Fireside Chat speakers, Jay Keasling and Kinkead Reiling, comes in. They were early pioneers in the field of metabolic engineering, the process of rewiring microorganisms to produce specific molecules. After an inspired set of initial experiments that managed to identify the metabolic pathway responsible for producing artemisinin (no small process), they set out to move this pathway into another host.

This involved the integration of a complex pathway with multiple genes into S. cerevisiae, baker’s yeast, a set of genetic modifications which were farther-reaching and more complex than any previously attempted.

What followed was years of work, the founding of Amyris, funding from the Bill & Melinda Gates Foundation, and a collaborative agreement with Sanofi-Aventis to produce the drugs at cost for the developing world.

This agreement is unique in a number of ways. The patents on the process have been licensed for no royalties, provided that they are used to provide artemisinin for the developing world. Sanofi-Aventis further agreed to sell this medicine for the costs of production, a no-profit-no-loss agreement. With distribution of these products occurring since August 2014, this agreement has already saved countless lives.

Breaking ground

From artemisinin, Amyris began to branch out into other fields, using their synthetic biology know-how to produce other chemicals. Next out of the lab was Biofene, the chemical farnesene produced via biological means, rather than as a petroleum secondary product. Today the company sells biologically produced diesel, jet-fuel, and cosmetic additives, with many products under development with industry partners.

In parallel to and in the same building as Amyris, Dr Keasling has run JBEI for the last decade with a focus on the production of bio-energy and chemical from renewable resources. Funded at $25 million a year since 2008, "JBEI is one of three DOE Bioenergy Research Centers (BRCs) established by DOE’s Office of Science in 2007 on the basis of a nationwide competition to accelerate fundamental research breakthroughs for the development of advanced, next-generation biofuels."The Fireside Chat Session between Jay Keasling and Kinkead Reiling will be from 11:55 pm – 12:25 pm at SynBioBeta SF.