Talk:CH391L/S13/Metabolic Engineering and Thermophiles

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*'''[[User:Gabriel Wu|Gabriel Wu]] 17:11, 15 April 2013 (EDT)''': The [http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12051.html latest] and greatest on the artemisinin project.
*'''[[User:Gabriel Wu|Gabriel Wu]] 17:11, 15 April 2013 (EDT)''': The [http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12051.html latest] and greatest on the artemisinin project.
*'''[[User:Dwight Tyler Fields|Dwight Tyler Fields]] 17:31, 15 April 2013 (EDT)''': From a big picture perspective, what are the boundaries on what one can get cells to produce? Maybe you could include this in a brief section on "future challenges" in the field?
*'''[[User:Dwight Tyler Fields|Dwight Tyler Fields]] 17:31, 15 April 2013 (EDT)''': From a big picture perspective, what are the boundaries on what one can get cells to produce? Maybe you could include this in a brief section on "future challenges" in the field?
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**'''[[User:Thomas Wall|Thomas Wall]] 10:22, 22 April 2013 (EDT)''': So this is a very hard thing to define, the limits to metabolic engineering are based on what enzymes you can find to do chemical reactions.  Research in metagenomics can mine out new enzymes for more and more reaction types.  In addition, protein engineering can be used to alter substrates enzymes can act upon.
*'''[[User:Evan J. Weaver|Evan Weaver]] 13:04, 16 April 2013 (EDT)''':  What makes thermophiles so hard to culture?  Is it because of the high heat in combination with the amount of pressure needed to keep them alive?
*'''[[User:Evan J. Weaver|Evan Weaver]] 13:04, 16 April 2013 (EDT)''':  What makes thermophiles so hard to culture?  Is it because of the high heat in combination with the amount of pressure needed to keep them alive?
**'''[[User:Aurko Dasgupta|Aurko Dasgupta]] 18:44, 16 April 2013 (EDT)''':I think thermophiles typically have a slower growth rate that mesotherms like ''E. coli''. ''[http://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans]'' (not a thermophile, but another kind of extremophile) takes 2-3 days to form decent sized colonies on plates. I think the difficulty of transformation is also partially due to differences in their exponential phase compared to normal bacteria.
**'''[[User:Aurko Dasgupta|Aurko Dasgupta]] 18:44, 16 April 2013 (EDT)''':I think thermophiles typically have a slower growth rate that mesotherms like ''E. coli''. ''[http://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans]'' (not a thermophile, but another kind of extremophile) takes 2-3 days to form decent sized colonies on plates. I think the difficulty of transformation is also partially due to differences in their exponential phase compared to normal bacteria.
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**'''[[User:Neil R Gottel|Neil R Gottel]] 18:58, 18 April 2013 (EDT)''':The wiki page for ''Pyrococcus furiosus'' says its doubling time at 100°C is 37 minutes, which is pretty quick. This might be an outlier though, since the species name ''furiosus'' refers to its (abnormally?) quick replication speed.
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**'''[[User:Benjamin Gilman|Benjamin Gilman]] 15:34, 18 April 2013 (EDT)''': Most of the species of bacteria out there are either difficult or impossible to grow in cultures, so it shouldn't be too shocking that thermophiles we've chosen for traits like novel metabolic pathways or ease of transformation don't also grow quickly.  The only ways to get over that are to engineer the bacteria for faster growth (which is hard), find a media condition that improves growth (less hard), or find a similar species that really likes growing in tanks (maybe impossible).
 +
**'''[[User:Max E. Rubinson|Max E. Rubinson]] 15:59, 18 April 2013 (EDT)''': I think I remember reading somewhere that thermophiles can be cultured more successfully when they are co-cultured with their natural symbionts.
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**'''[[User:Thomas Wall|Thomas Wall]] 10:33, 22 April 2013 (EDT)''':  These organisms typically are in aquatic environments with a complex chemical makeup compared to even your standard aquatic microbes.  Ben pretty much filled in the rest. 
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*'''[[User:Gabriel Wu|Gabriel Wu]] 23:07, 17 April 2013 (EDT)''': What's the cost-benefit of maintaing a higher culturing temperature versus using other forms of selection? I know antibiotics at industrial scale are cost prohibitive. What selection is used currently and is it really cheaper to just keep cultures at 50°C?
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**'''[[User:Thomas Wall|Thomas Wall]] 10:56, 22 April 2013 (EDT)''':  Well it really depends on the value of the chemical you are making, but a top dollar value chemical target would be necessary to warrant antibiotic use.  However, this is just never really necessary for a production facility, as one can generally make auxotrophs.  Antibiotics are great for proof of concept work while the strains are being designed and are phased out in the final production strains.  I can't find a source, but I imagine that with a well insulated reactor that this is a negligible expense.
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*'''[[User:Yunle Huang|Yunle Huang]] 15:26, 18 April 2013 (EDT)''':Perhaps you can expand on precisely how some of the "Modern techniques" can be used in metabolic engineering? Maybe expands on some of the examples you gave in that section.
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**'''[[User:Thomas Wall|Thomas Wall]] 12:56, 22 April 2013 (EDT)''':  Tried to elaborate more, maybe it's helpful, let me know.

Current revision

  • Gabriel Wu 17:11, 15 April 2013 (EDT): The latest and greatest on the artemisinin project.
  • Dwight Tyler Fields 17:31, 15 April 2013 (EDT): From a big picture perspective, what are the boundaries on what one can get cells to produce? Maybe you could include this in a brief section on "future challenges" in the field?
    • Thomas Wall 10:22, 22 April 2013 (EDT): So this is a very hard thing to define, the limits to metabolic engineering are based on what enzymes you can find to do chemical reactions. Research in metagenomics can mine out new enzymes for more and more reaction types. In addition, protein engineering can be used to alter substrates enzymes can act upon.
  • Evan Weaver 13:04, 16 April 2013 (EDT): What makes thermophiles so hard to culture? Is it because of the high heat in combination with the amount of pressure needed to keep them alive?
    • Aurko Dasgupta 18:44, 16 April 2013 (EDT):I think thermophiles typically have a slower growth rate that mesotherms like E. coli. Deinococcus radiodurans (not a thermophile, but another kind of extremophile) takes 2-3 days to form decent sized colonies on plates. I think the difficulty of transformation is also partially due to differences in their exponential phase compared to normal bacteria.
    • Neil R Gottel 18:58, 18 April 2013 (EDT):The wiki page for Pyrococcus furiosus says its doubling time at 100°C is 37 minutes, which is pretty quick. This might be an outlier though, since the species name furiosus refers to its (abnormally?) quick replication speed.
    • Benjamin Gilman 15:34, 18 April 2013 (EDT): Most of the species of bacteria out there are either difficult or impossible to grow in cultures, so it shouldn't be too shocking that thermophiles we've chosen for traits like novel metabolic pathways or ease of transformation don't also grow quickly. The only ways to get over that are to engineer the bacteria for faster growth (which is hard), find a media condition that improves growth (less hard), or find a similar species that really likes growing in tanks (maybe impossible).
    • Max E. Rubinson 15:59, 18 April 2013 (EDT): I think I remember reading somewhere that thermophiles can be cultured more successfully when they are co-cultured with their natural symbionts.
    • Thomas Wall 10:33, 22 April 2013 (EDT): These organisms typically are in aquatic environments with a complex chemical makeup compared to even your standard aquatic microbes. Ben pretty much filled in the rest.
  • Gabriel Wu 23:07, 17 April 2013 (EDT): What's the cost-benefit of maintaing a higher culturing temperature versus using other forms of selection? I know antibiotics at industrial scale are cost prohibitive. What selection is used currently and is it really cheaper to just keep cultures at 50°C?
    • Thomas Wall 10:56, 22 April 2013 (EDT): Well it really depends on the value of the chemical you are making, but a top dollar value chemical target would be necessary to warrant antibiotic use. However, this is just never really necessary for a production facility, as one can generally make auxotrophs. Antibiotics are great for proof of concept work while the strains are being designed and are phased out in the final production strains. I can't find a source, but I imagine that with a well insulated reactor that this is a negligible expense.
  • Yunle Huang 15:26, 18 April 2013 (EDT):Perhaps you can expand on precisely how some of the "Modern techniques" can be used in metabolic engineering? Maybe expands on some of the examples you gave in that section.
    • Thomas Wall 12:56, 22 April 2013 (EDT): Tried to elaborate more, maybe it's helpful, let me know.
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