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Fascinating! This is a completely new area to me. Can I ask what the advantage of this over "classical" biosynthesis pathways, where precursors float from one e

by biofox 2y ago

Fascinating! This is a completely new area to me. Can I ask what the advantage of this over "classical" biosynthesis pathways, where precursors float from one enzyme to another?

_yb2s 2y ago
They have different strengths and weaknesses, and natural product pathways often naturally combine steps from both. I'm not sure how technical to make this, but from your username and comments I will assume I can make it pretty technical. Some of the advantages of PKSs (both for bioengineering, and for the microbes using them to make molecules): -Rapid evolution and/or engineering modifications: the predictable relationship between the DNA and resulting chemical structure means you can reliably change the DNA and know what will happen to the chemical structure. This reconfigurability is also useful for microbes- they can duplicate or delete regions of DNA to create new variants, such as new antibiotics when their competition develops resistance. -You can change a part of the molecule without having to have anything unique in that region that an enzyme will recognize to act in the right spot- because a specific region of the assembly line relates to a specific part of the final product. -Avoids a lot of the issues of enzyme promiscuity in engineered pathways, to make something really different from what exists naturally while reusing natural domains. Although PKS domains can be selective, can be promiscuous and still work (and many natural ones are), because the physical configuration of the PKS will only present them with the right substrate at the right time -Overcomes lots of issues with reactant concentrations, and thermodynamics. Because the substrate is physically tethered, it is channeled right to the reaction site, and then snatched away afterwards- effectively simulating a very high reactant concentration, and a low product concentration, allowing reactions to occur in the right direction, that wouldn't otherwise be favorable/spontaneous -Precise control over stereochemistry There are also NRPSs, which are similar to PKSs, but make peptides instead of polyketides...
- biofox 2y ago
  Thank you!

by biofox 2y ago

Fascinating! This is a completely new area to me. Can I ask what the advantage of this over "classical" biosynthesis pathways, where precursors float from one enzyme to another?

_yb2s 2y ago

They have different strengths and weaknesses, and natural product pathways often naturally combine steps from both. I'm not sure how technical to make this, but from your username and comments I will assume I can make it pretty technical. Some of the advantages of PKSs (both for bioengineering, and for the microbes using them to make molecules): -Rapid evolution and/or engineering modifications: the predictable relationship between the DNA and resulting chemical structure means you can reliably change the DNA and know what will happen to the chemical structure. This reconfigurability is also useful for microbes- they can duplicate or delete regions of DNA to create new variants, such as new antibiotics when their competition develops resistance. -You can change a part of the molecule without having to have anything unique in that region that an enzyme will recognize to act in the right spot- because a specific region of the assembly line relates to a specific part of the final product. -Avoids a lot of the issues of enzyme promiscuity in engineered pathways, to make something really different from what exists naturally while reusing natural domains. Although PKS domains can be selective, can be promiscuous and still work (and many natural ones are), because the physical configuration of the PKS will only present them with the right substrate at the right time -Overcomes lots of issues with reactant concentrations, and thermodynamics. Because the substrate is physically tethered, it is channeled right to the reaction site, and then snatched away afterwards- effectively simulating a very high reactant concentration, and a low product concentration, allowing reactions to occur in the right direction, that wouldn't otherwise be favorable/spontaneous -Precise control over stereochemistry There are also NRPSs, which are similar to PKSs, but make peptides instead of polyketides...

biofox 2y ago
Thank you!