Comments on: Combining MAGE and synthetic metagenomics for bio-manufacturing http://blog.ginkgobioworks.com/2009/08/10/combining-mage-and-synthetic-metagenomics-for-bio-manufacturing/ By Ginkgo BioWorks Sat, 31 Jul 2010 19:20:48 +0000 http://wordpress.org/?v=2.7 hourly 1 By: Reshma http://blog.ginkgobioworks.com/2009/08/10/combining-mage-and-synthetic-metagenomics-for-bio-manufacturing/comment-page-1/#comment-7112 Reshma Wed, 19 Aug 2009 12:29:15 +0000 http://blog.ginkgobioworks.com/?p=178#comment-7112 I agree. With better DNA construction technologies like DNA synthesis, MAGE, and DNA assembly, the bottleneck in the pipeline moves from construction to screening and testing. High throughput culture growth followed by GC analysis is a doable but imperfect solution. If only there was some lab working on developing <em>in vivo</em> sensors of metabolites that could be connected to a reporter system to enable visual screening of colonies for any compound of interest. ;) I agree. With better DNA construction technologies like DNA synthesis, MAGE, and DNA assembly, the bottleneck in the pipeline moves from construction to screening and testing. High throughput culture growth followed by GC analysis is a doable but imperfect solution. If only there was some lab working on developing in vivo sensors of metabolites that could be connected to a reporter system to enable visual screening of colonies for any compound of interest. ;)

]]> By: Josh http://blog.ginkgobioworks.com/2009/08/10/combining-mage-and-synthetic-metagenomics-for-bio-manufacturing/comment-page-1/#comment-7001 Josh Wed, 12 Aug 2009 20:32:18 +0000 http://blog.ginkgobioworks.com/?p=178#comment-7001 What you're missing is the screening strategy. MAGE can generate mutants, but you still need to pick out the best ones. The Voigt lab synthesized ~80 enzymes, and could characterize each one individually. The Church lab constructed millions of mutants and screened (by eye, based on color) ~10,000 of those. Neither approach is particularly scalable/generalizable. What you’re missing is the screening strategy. MAGE can generate mutants, but you still need to pick out the best ones. The Voigt lab synthesized ~80 enzymes, and could characterize each one individually. The Church lab constructed millions of mutants and screened (by eye, based on color) ~10,000 of those. Neither approach is particularly scalable/generalizable.

]]> By: Chris Edwards http://blog.ginkgobioworks.com/2009/08/10/combining-mage-and-synthetic-metagenomics-for-bio-manufacturing/comment-page-1/#comment-6976 Chris Edwards Tue, 11 Aug 2009 12:24:24 +0000 http://blog.ginkgobioworks.com/?p=178#comment-6976 If it helps, I've written up a description of MAGE here: http://blog.thebiomachine.com/2009/07/harvard-hits-the-fast-forward.html The interesting thing about MAGE is the way it combines a form of directed evolution by using degenerate sequences coupled with targeted mutations. It also neatly complements large-scale gene synthesis by allowing edits to be made throughout a genome more cheaply, just as long as the total percentage of changes is quite low. One thing I think MAGE offers genetic part-based design is the ability to tune up RBS and promoter sites after a module has been assembled. If a promoter or RBS is not quite working out, use the degenerate replacements to find better 'matches'. If it helps, I’ve written up a description of MAGE here: http://blog.thebiomachine.com/2009/07/harvard-hits-the-fast-forward.html

The interesting thing about MAGE is the way it combines a form of directed evolution by using degenerate sequences coupled with targeted mutations. It also neatly complements large-scale gene synthesis by allowing edits to be made throughout a genome more cheaply, just as long as the total percentage of changes is quite low.

One thing I think MAGE offers genetic part-based design is the ability to tune up RBS and promoter sites after a module has been assembled. If a promoter or RBS is not quite working out, use the degenerate replacements to find better ‘matches’.

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