Dr Andrew Hanson, University of Florida
Metabolism's dark underside – and what SynBio has to fear from it
Metabolic biochemists and engineers tend to idealize metabolism as a network of inherently efficient pathways mediated by perfectly specific enzymes. This ‘pathway-centric’ thinking is inadequate for metabolic SynBio because it neglects metabolism’s dark underside, i.e. three inescapable but often overlooked truths: (i) Metabolites undergo damaging chemical and enzymatic side-reactions in vivo; (ii) The products of these reactions are wasteful or actively harmful, and (iii) Organisms have powerful systems to limit buildup of such damage products. These damage-control systems return damaged molecules to their original state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Without the appropriate damage-control systems, a metabolic pathway may not function efficiently or even at all. Thus installing a non-native pathway in a platform organism always runs some risk of failure because the platform lacks the right damage-control systems. The more alien the pathway, the bigger the risk. This risk is even bigger in cell-free SynBio.