Dear Wenhe,

>From my perspective you have quite a few options. Notably, the presence of
glycosylation in the native host does not always (or even often) mean that
you *must* have the protein in the native glyco-state in order to be
'right'. Very often glycosylation sites can be trimmed (by e.g. Kifunensine
and similar compounds) or mutated out. When one mutates glycosylation sites
one runs a significant risk of stopping export - meaning that without
correct glycosylaton some proteins do not secrete. This is very much
protein dependent and host dependent but I have personally experienced
about a dozen cases (out of hundreds which went just fine). So it's not a
#1 item to be scared of.

Options:

1. refold from IB in E. coli
2. secrete into periplasm in E. coli
3. secrete into media from a gram-positive organism (e.g. Bacillus)
4. secrete from yeast
5. secrete from insect cells
6. secrete from mammalian cells

For you it seems that 5 and  6 may be a bit of an overkill, but it all
depends on the nature of the protein you're working with :) I normally
recommend 1 and 6 to 'bracket' the probability spread (1 is very easy but
often not very successful whereas 6 is expensive but is often very
successful, and both are very fast).

Artem

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On Wed, Jul 11, 2018 at 11:54 PM, WENHE ZHONG <[email protected]>
wrote:

> Dear Community,
>
> A little bit out of topic here. An enzyme we like to use in our assay is
> commercially available. However, we found some unfavorable activities that
> probably from the contaminants from this commercial source. We checked the
> company website and found out this enzyme was purified from the original
> organism without tag for enhancing purification. No purity data was shown
> as well.
>
> So we want to see whether we can produce the recombinant protein with tag.
> After checking the literatures, this enzyme is a N-linked glycosylated
> protein (glycan attached to 3 asparagine residues) and is from
> fungi Penicillium citrinum. These 3 glycosylations probably affect protein
> folding, stability and its location in the cell. Currently we have three
> options here:
>
> 1. Express this enzyme in yeast which is a similar system compared to
> Penicillium citrinum. His6 tag will be added to the N- or C- terminal of
> this protein.
> 2. Express this enzyme in the periplasm of E.coli. However, no
> glycosylation system in E.coli. Only one paper published in a not well
> known journal used this method. But the result is not very conclusive to
> us. If their claim is correct, the glycosylation at this enzyme is not
> essential for protein production.
> 3. Express this enzyme in insect cells. More complicated and advanced
> glycosylation system in insect cells compared to fungi.
>
> Anyone has experience with glycoprotein? It will be very helpful if I can
> have your advice. Thank you.
>
> Kind regards,
> Wenhe
>
>
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