3 ms·

These type of proteins "PKSs" are one of the most promising and exciting areas of biotech research. They offer a path to make a sort of programmable biochemical

by _yb2s 2y ago

These type of proteins "PKSs" are one of the most promising and exciting areas of biotech research. They offer a path to make a sort of programmable biochemical factory, where bacteria can make a custom drug, plastic polymer, etc. in a predictable way. They can also do some tricky chemistry that is almost impossible any other way. PKSs build a molecule piece by piece like a car assembly line, and follow a predictable logic where you can tell from the parts in the DNA exactly what chemical they will make. After 30+ years of working on it bioengineers are finally figuring out how to reliably mix and match the parts to make custom PKSs that work.

elric 2y ago
Can you elaborate on the reliability of the process? I imagine there are a lot of things that could go wrong when applying biological processes at any scale where they are able to produce meaningful quantities of stuff?
- _yb2s 2y ago
  There are two main obstacles: actually making a new molecule with a PKS, and getting it to be active enough to make useful and financially viable quantities of a product. Both are challenging. A substantial fraction of the currently used pharmaceuticals, especially big complex antibiotics are already made commercially at scale with PKSs- but mostly in cases where they are just using the natural organism with its natural PKS. They are challenging to engineer, e.g. "get parts to work together" in an unnatural order but that has been getting better over time, with lots of recent breakthroughs, and a bunch of new molecules being made, but the production quantities do tend to be low. There is no fundamental reason why PKSs have to be slow, or make small quantities of things, there are a few good examples of both natural products and engineered PKSs that make things in really high concentrations. So this is presumably something that can be improved over time, but is definitely the biggest weakness, which limits commercial viability right now to high value things like drugs.
ramraj07 2y ago
Can you elaborate on What’s a PKS? Have you read the science article and does it mention PKS? I don’t have full text access but from the article and the abstract it didn’t sound like it’s a new addition to an existing paradigm..
- _yb2s 2y ago
  A PKS is a "polyketide synthase" which is a type of enzyme that acts sequentially, like an assembly line to build large complex molecules. It is best visualized- there are some good videos on youtube with animations and figures showing how they work. Yes, I read the article- polyketide synthase (PKS) is mentioned right in the title. What makes this finding novel is just how massive this PKS, named PKZILLA is compared to previously discovered ones.

by _yb2s 2y ago

elric 2y ago

Can you elaborate on the reliability of the process? I imagine there are a lot of things that could go wrong when applying biological processes at any scale where they are able to produce meaningful quantities of stuff?

_yb2s 2y ago
There are two main obstacles: actually making a new molecule with a PKS, and getting it to be active enough to make useful and financially viable quantities of a product. Both are challenging. A substantial fraction of the currently used pharmaceuticals, especially big complex antibiotics are already made commercially at scale with PKSs- but mostly in cases where they are just using the natural organism with its natural PKS. They are challenging to engineer, e.g. "get parts to work together" in an unnatural order but that has been getting better over time, with lots of recent breakthroughs, and a bunch of new molecules being made, but the production quantities do tend to be low. There is no fundamental reason why PKSs have to be slow, or make small quantities of things, there are a few good examples of both natural products and engineered PKSs that make things in really high concentrations. So this is presumably something that can be improved over time, but is definitely the biggest weakness, which limits commercial viability right now to high value things like drugs.

ramraj07 2y ago

Can you elaborate on What’s a PKS? Have you read the science article and does it mention PKS? I don’t have full text access but from the article and the abstract it didn’t sound like it’s a new addition to an existing paradigm..

_yb2s 2y ago
A PKS is a "polyketide synthase" which is a type of enzyme that acts sequentially, like an assembly line to build large complex molecules. It is best visualized- there are some good videos on youtube with animations and figures showing how they work. Yes, I read the article- polyketide synthase (PKS) is mentioned right in the title. What makes this finding novel is just how massive this PKS, named PKZILLA is compared to previously discovered ones.