Gabriel Wu 03:42, 13 February 2013 (EST): In principle, a minimal genome that has just enough genes for a cell to grow and divide sounds good. I wonder how reliable and stable this chassis might actually be though. What if removing all the "redundant" pathways results in a fragile cell where the addition of new genes results in cell non-viability? For example, biofuel products are notoriously toxic to the cell. If a bottom up approach is taken by starting with a minimal genome and then inserting ethanol genes, the minimal genome cell will likely never grow up due to alcohol toxicity. If engineering is an iterative process, it may be difficult to optimize no growth. Sometimes it's easier to start with a cell that can tolerate small amounts and then knock in or out whichever genes are needed to improve tolerance.
- Neil R Gottel 15:55, 13 February 2013 (EST):An iterative approach: start with a low-expression version of your ethanol production construct that reduces growth, but doesn't kill the cell. Then, start adding in ethanol tolerance genes, looking for increases in the growth rate. Then bump up the expression of the ethanol gene again, and tweak the ethanol resistance again. Question is: will the end result of this be better than starting with a non-minimized, ethanol resistant cell? And how long would each approach take?
- Gabriel Wu 01:45, 14 February 2013 (EST): I would be surprised if the bottom-up approach would be faster than top down. Also, if we knew all the interactions among ethanol tolerance genes, we might not need the bottom up approach to begin with. Also, are ability to "bump up" expression levels is less than well understood.
Neil R Gottel 17:25, 12 February 2013 (EST):I recommend that the work of the Blattner Lab on clean E. coli genomes should feature prominently in this article, since that's the state-of-the-art right now, and is a commercial product sold by Scarab Genomics. Is there a version of that sweet graphic that shows the deleted regions on the genome that we're allowed to use, because that'd be a great addition.
Neil R Gottel 17:25, 12 February 2013 (EST):At some points this article has turned into a wall of text, particularly for the section on estimating the number of essential genes. I think it'd be helpful if a few people took a subheading and cleaned it up (and documented what they did here). For my part, I rewrote the section on "Genome Synthesis".