Manufacturing is already an area of demonstrable success in synthetic biology. It is built on a diverse history of work on metabolic pathway engineering starting in the early 1980's, with projects such as the production of human insulin using recombinant DNA technologies. A well-known current example is Amyris' engineering of the antimalarial drug precursor, artemisinic acid. Other companies are demonstrating the production of transportation fuels using algal systems in photobioreactors on non-arable land.
Manufacturing will also play a big role in tissue engineering through the production of new skin, organs and other medical substrates to treat disease and injury. While these problems may seem like medical technologies, scaling them up from the bench to the clinic will require significant innovations in manufacturing.
The potential for the manufacturing track in iGEM is immense. Biological systems can be used to make products under conditions that were previously impossible. Many enzymes can achieve reaction conditions in a tube that would otherwise require high temperatures, pressures or expensive substrates to reproduce using chemical engineering methods. Another possibility is micro-scale production of drugs, therapeutics or other high-value molecules. iGEM teams who choose to work on manufacturing have a wide range of possible projects and many large challenges to overcome.
You can find images and abstracts of the winning Manufacturing track teams from 2015 to 2016 below.
biotINK - rethINK tissue printing
Living in an aging society and facing the increasing organ shortage, we have developed a game-changing approach to bioprint tissues for biomedical application. Our interdisciplinary work entails creating a novel bioink that exploits the rapid and specific interaction of biotin and its tetrameric binding protein streptavidin. By employing this affinity, we have engineered cells presenting biotin moieties or biotin binding proteins on their surfaces and recombinant biotinylated proteins as spacer molecules, which both co-polymerize upon contact with streptavidin. Furthermore, we have explored different cellular circuits, which allow us to control pancreatic cell lines, induce tissue vascularization, or install biosafety mechanisms for printed tissues. To deliver these cells, we employ a hijacked 3D printer that enables us to manufacture three-dimensional multi-cellular structures in a user-definable manner. Altogether, we are confident that our system provides the necessary means to advance the SynBio community to the next level – the tissue level.
Escherichia coli expression systems, promoter and gene optimization.
Our group aims to generate sugar-induced expression system for Escherichia coli, which consists of promoters induced by arabinose, rhamnose, xylose and melibiose. The system is tightly regulated, provides independent induction of at least two different promoters and can be efficiently blocked by glucose. We have introduced various modifications of promoter sequences to obtain minimal, fully functional promoters, possibly stronger than original versions copied from E. coli genome. The modifications include changes in 5'UTR regions, likely ribosome binding sites and secondary structures to evaluate how those features affect translational machinery. We have also focused on open reading frame (ORF) optimization. Using bioinformatic analysis we have created sfGFP and mRFP variants composed exclusively of the most frequent or the rarest codons. We have also designed ORFs to control codon context effects and GC content for evaluation of their influence on translational effectiveness.
Upcycling Methanol into a Universal Carbon Source
Nowadays, mankind uses 94 million barrels of oil per day. But as agreed on by various nations, we have to become independent from fossil resources during the next decades. As a consequence, not only fuels, but many other products including drugs, fine chemicals and plastic will have to be produced from renewable carbon sources. In parallel, we observe arable land per capita shrinking and more frequent droughts. But even by increasing agricultural productivity, plants will not be able to meet our massive demands. Therefore, we are developing an alternative route to sustainably produce complex carbon which significantly reduces the space and water needs. By using new synthetic pathways, we are upcycling a simple, renewable chemical into a universal carbon source.
biOrigami: A New Approach to Reduce the Cost of Space Missions
Space exploration lies at the inquisitive core of human nature, yet high costs hinder the advancement of this frontier. We are harnessing the replicative properties of biology to create biOrigami—biological, self-folding origami—to reduce the mass, volume, and assembly time of materials needed for space missions. biOrigami consists of two main components: manufacturing substrates biologically and bioengineering folding mechanisms. For substrates, we are developing new BioBricks to synthesize two thermoplastics: polystyrene and polyhydroxyalkanoates. For folding mechanisms, we are using heat-induced contraction of thermoplastics and the contractile properties of bacterial spores. After consulting with experts, we believe that biOrigami could be incorporated into rovers, solar sails, and more. In addition to biOrigami, we are creating a novel method to efficiently transform bacteria by using the CRISPR/Cas9 system, benefitting the broader synthetic biology community. Our project integrates and improves manufacturing processes for space exploration on both the micro and macro levels.