In general terms, synthetic biology brings to mind using “BioBricks”, which are engineered genetic parts used to modify an organism, such as bacteria or yeast. The idea is to modify the organism to work to our advantage; for example, to eat sugar and produce biofuel — a pretty good tradeoff, considering the cost of gasoline and the cost of sugar. This is a top-down methodology: take an existing organism, modify it’s DNA, measure it’s behavior, and repeat the modification process until the desired “behavior” is measured.
Some synthetic biology research, however, doesn’t use traditional organisms at all. In fact, doesn’t even use “cells”. This might be called cell-free synthetic biology, or in vitro synthetic biology. This is a bottom-up approach: create the desired “behavior” from scratch. The idea has existed for some time; a good summary is Synthetic biology projects in vitro, Anthony C. Forster and George M. Church, Genome Res. 17:1-6, 2007: “Many biopolymer syntheses are already better scaled up in cell-free systems, such as linear DNAs by oligo synthesis and PCR, unmodified RNAs by in vitro transcription, and peptide libraries by in vitro transcription/translation. And engineering flexibility is much greater in vitro, unshackled from cellular viability, complexity, and walls.”
“How can I hack biology without using cellular organisms?”, you’re probably asking.
One proposed method for creating such cell-free synthetic biology projects (meaning: no bacteria, no yeast… just… chemistry) is An integrated cell-free metabolic platform for protein production and synthetic biology, Michael C Jewett, Kara A Calhoun, Alexei Voloshin, Jessica J Wuu & James R Swartz, Molecular Systems Biology 4:220. These fully synthetic systems have significant environmental interactions in common with traditional bacteria:
It is striking to note that the Cytomim system closely mimics E. coli cellular metabolism. It is homeostatic in pH and [Pi], uses natural, non-phosphorylated energy substrates, provides a long-lasting ATP source, and fuels highly productive protein synthesis (up to 600 mg protein/l/h). In addition, each ribosome can polymerize approximately 10 500 amino acids (42 copies of chloramphenicol acetyl transferase, CAT), indicating that the Cytomim system is not limited by enzyme turnover (e.g. only one protein, or fraction of a protein, produced per ribosome). Furthermore, the specific oxygen uptake rate in the Cytomim system is on the same order as for intact E. coli cells.
As can be seen from the date of this publication (2008), this research is cutting edge. Prior work by the same primary author established this Cytomim system.
Digital-logic-like bistable circuit using synthetic biology without using organisms has previously been described in Construction of an in vitro bistable circuit from synthetic transcriptional switches, Jongmin Kim, Kristin S White & Erik Winfree, Molecular Systems Biology 2:68
The question by now might have changed. Maybe at this point, you are asking, “Why should I use extensive trial-and-error while attempting to modify existing bacteria, when I can create exactly the proteins I need, from the ground-up, instead?”
That’s a good question for further research.