Mutasynthetic biotransformations

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Video in TIB AV-Portal: Mutasynthetic biotransformations

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Title
Mutasynthetic biotransformations
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CC Attribution - NoDerivatives 4.0 International:
You are free to use, copy, distribute and transmit the work or content in unchanged form for any legal purpose as long as the work is attributed to the author in the manner specified by the author or licensor.
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Publisher
Release Date
2012
Language
English

Content Metadata

Subject Area
Abstract
We describe the unprecedented formation of six ansamitocin derivatives that are deoxygenated at C-7 of the ansamitocin core. The ansamitocin core is obtained by fermentation experiments that employ a variety of Actinosynnema pretiosum mutants and mutasynthetic approaches. The video shows in detail how the mutasynthetic experiments are conducted. Additionally, the antiproliferative test of the new ansamitocin derivatives is shown.
Keywords catalysis
Naturstoff Organische Chemie Functional group Biotransformation
Naturstoff Chemical structure Library (computing) Derivative (chemistry)
Biosynthesis Organische Chemie Chemical structure Nanoparticle Multiprotein complex
Naturstoff Synthetic oil Organische Chemie Recreational drug use Lactitol Totalsynthese Atom Chemist Chemistry
Organische Chemie Functional group Chemist
Enzyme Metabolic pathway
Molecule Naturstoff Recreational drug use
Semiotics Molecule Ring strain Organische Chemie Enzyme Metabolic pathway Gene Sea level Genome Chemist
Naturstoff Metabolic pathway Toll-like receptor Derivative (chemistry)
Organische Chemie Gemstone Totalsynthese Chemist
PH indicator Chemical experiment Storage tank Thermalquelle Solution
Chemical experiment
Chemical experiment
Sample (material) Organische Chemie Chemical experiment
Chemical experiment
Chemical experiment Wursthülle
Chemical experiment
Chemical experiment Mixture Chemical reaction
Chemical experiment Growth medium
Chemical experiment
Chemical experiment Solution
Blood vessel Chemical experiment Solution Steroid
Chemical experiment Chemical compound Steel Electronic cigarette
Flocculation Feed (film) March (territory) Chemical experiment Cultivator Growth medium Periodate
Chemical experiment
Water purification Molecule Systemic therapy Cell division Human subject research Cell (biology) Chemical experiment Chemical compound Alkoholische Gärung Wine tasting descriptors
Molecule Chemical experiment Derivative (chemistry) Alcohol
Metal Activity (UML) Chemical compound Toll-like receptor
Famotidine Cell (biology) Chemical experiment Growth medium Controller (control theory) Chemical compound
Chemical experiment
Cell (biology) 3'-Phosphoadenosine-5'-phosphosulfate Chemical experiment Arzneimitteldosis Beta sheet Thermoforming
Deterrence (legal) Synthetic oil Chemische Synthese Metabolic pathway Synthetic biology Substrat <Chemie> Gene cluster Stiffness
Organische Chemie ISO-Komplex-Heilweise Biotransformation Molecularity Chemistry Hydrophobic effect Collision
the agency to organic chemistry with a lighted seems to have my name is under his kitchen sink in and having a research group that is dedicated to natural products in this field we are particularly interested in developing new strategies and tech.
six. to create natural puck derivatives or even small libraries and the natural products that we usually handle structure rather complex so they are very difficult to access by synthetic purely synthetic methods on the other hand all of our national parks logically very relevant and also pharmacologically highly potent.
but we look at natural particles how they have flown by nature and nature's pursues a highly effective and specific and precise multistep by a synthesis to create structural complexity synthetic organic chemistry however is very flexible you can introduce easily fluorine into a.
natural product by total synthesis which is very difficult for nature to achieve however flowing is an important hatred atom in missile chemistry and the development of drugs do not base our work specifically on purely chemical knowledge but rather look in neighbouring disciplines such as in.
engineering and biology look for status methods and techniques there and try to introduce and implement them into the portfolio of the synthetic again the chemist the new term that is important to mention here is meters into says it basically uses engine it organisms the produce of.
that and natural products like and the might assign and combines it with chemicals and this is peaceful me and take a look at the theoretical aspects of years and this is as well as take a look at how this is transformed into a laboratory environment particularly the border environment that is rather can. mikel. hello my name is for khan and communal research group leader to institute of organic chemistry here in or i'm going to introduce you into a concept of new justices the present publication deals with and some might have since and the viruses of hands on my distance is arranged in the stepwise assembly line like question.
we have several intermediates you into by us into the pathway and each intermediate is in the converted into it or by the particular enzyme for example intermediate a reacts with amazon a two intermediate be rex was as i'm be two intermediate see and so on.
on and finally when up with a very complex natural products starting from very simple because of molecules one of these because the more you could is a mean or drugs have been so i guess it h.p.a..
so nobody's is also possible to menu printed by us into the path was on the genetic level for example from huge distances we remove or disrupt genes from the genome this leads to changes in the bias into says if we for example removed the genes for enzyme a the organism is no longer able to produce into. you'd be we have a so-called marcotte strain or blocked mutant what we now do is we feed the symbol oprah cause a molecule called might have enjoyed as it so we feed to block to constrain and see what happens so would have been something which is quite interesting for a chemist because this.
derivative of the preachers it is accepted by the bias into the pathway so it is channelled through it to buy out different intermediates which are not identical very similar to ones from the native pathway and finally end up new natural product derivative so we end up with death toll.
see just floral. coral and some might us and so does a very attractive opportunity for chemist to hand over the endgame of a total synthesis to an organism i will not hand over to get it too will show you for such an experimental stone in practice.
if health i get a year in and today i will show you how we actually perform you to think that this indication do so first what we need is all microorganism acting as an m a pretty awesome is a spark of eighteen a bacterium and can usually keep its stores as a spa solution.
in minus eighty degrees and first now i will put those force on one are complete i use regular toothpicks which just are licensed.
and then draw narrow lines on to the art of the.
after applying them on the other being cubism for seven days in the division but twenty years.
so over here i've prepared to sample which is roughly forty five did all for you can see it's not completely grown yet but over here you can see the orange central park is the living organism why the am i see them on the edges of the colonies consists mainly of.
this force so for the inoculation we only to the m i see them so in this case use you know relation to sterilise that.
and take up some of the n.y.c. them.
and put this am i see them into.
the reaction wrestle with glass beads and wonderful.
and then voted for the whole mixture to suspend the force in the war.
and then we can at these was put to the pre culture medium to inoculate this is then incubated for to the twenty eight degrees and afterwards we can use these precautions on to inoculate mean cultures where we use a special production you.
which is optimized for the production of second remarkable life's sought after that we have all mean cultures which routine too big for another two days and after another to these will at the top street which synthesize four.
and we still need to steer i feel today so we take off. the solution.
in a slowing. even use a steer i filter.
to feel good with a mission into another vessel.
this steroids solution can then be taken up into law syringe which can then be attached to.
to be free.
we attach it to go so intrigued almost the right solution and at the end we can attach own steel annual this can then be put through these are caught in black and we can at the compound continuously all the previous home to the culture.
the media which is in the march because usually you can only do this you know them by react. over to you can see a typical feeding exponent will be for women in the distant from bias so the engine the upper part in the soviet economy would have to get into all for cultivation flocks and we at it over a period of three d. very slowly.
and then afterwards the that have been on other to the up the which we can actually take up the whole of divisions lost and will work on. after fermentation we need to obtain our compound and we do that by extracting the fermentation proper the deficit to this obtain crew product is then feel total the civic a pet to get rid of most of the cell fragments and in order to get rid of micro molecules that pool.
teens or should with the use of subjects system a chill twenty which you can see on the right hand side and this retains all compound and the especially small molecules and after that we just need to find a purification by hot h.b.o. seek to obtain all find compound.
what we would expect is this molecule which have gone with you but we didn't find the small accuse the phone other derivatives which a modified much so in fact this is a pro and the much the same derivative which doesn't have these functionalities. ten. but the more important thing is that actually this modified in this column loyalty so actually one very important that it if he's the one where doesn't have a column with loyalty at all.
and we can find that keeps on over here and compete reduced alcohol to the archive do so this is one important component and the other one which we phoned. was way you got it.
reduced the toll which is then problem with it. those two compounds i special interesting because they have both modified in this region where we usually have to cover more annoyed to which is essential for biological activity and it's why it's also very interesting to evaluate these compounds in biological testing.
my name is working. i wanted to get them to the f.a. is an establishment the metal the middle but it. it is based on the doctrine of the two and to do so much time sold the advantage of this as it is the comparison of the middle been a bit too good to have known for writing and great and so a frosty celled i could to greater than ninety six were played it was compound and different course.
the duration is headed and to test compound was outsells is used as a control. the cells are then incubated five days it's good to seven degrees and to this time the medium is move.
now a freshman year was tempted to serve as ever.
and now sells in beta again for two hours and debate. just say i through pap one place for you so you can see those odds the number of living cells called lies directly to the amount of the blue for months on sold so now you can quantify it's a form of thoughts old was michael page freedom from this was ousted we can calculate a dose dependent court.
i believe in the future research has to focus on improve many place of by synthetic pathways in order to broaden the sub substrate specificity of these by synthetic gene clusters in order to get the full scope of flexibility synthetic chemistry as well as synthetic biology.
she has to be combined in order to create a larger structural space to be addressed. i thank you for attention.
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