Have you tried adding a detergent such as SDS to your cells when you lyse them? 
This in my experience helps improve the soluble fraction significantly although 
it may lead to downstream problems with removal of the detergent.

From: xaravich ivan [mailto:[email protected]]
Sent: 17 October 2014 02:52 PM
To: [email protected]
Subject: [ccp4bb] Strategies to bring out over-expressed protein from inclusion 
bodies to soluble fraction!!!

Dear cc4bb enthusiasts,
This is slightly off topic but many protein crystallographers might be familiar 
with this problem.
I have been trying to over-express a bacterial (non-E.Coli) protein  in E.Coli 
and more than 80% goest to inclusion bodies.

I tried the following
Lowering the IPTG concentration to 0.1mM (range test from 0.075 mM - 0.5 mM)
Cold shock for 30 minutes in ice before induction
Slow rotation speed at 18 degrees O/N after induction
While these steps helped a bit I still get about 50-60% of my protein in 
inclusion bodies.
I would like to know what other steps do you suggest to enhance the yield in 
the soluble fraction (without changing the host strain or manipulating the DNA)
Thanks in advance
Ivan

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