Comprehensive Overview of Terpenoid Biosynthesis via MVA and MEP Pathways

[Music] [Music] welcome to nptl online certification

course on pharmacognosy and metabolic engineering uh we'll now discuss uh biosynthesis of tarpo and outline in

this lecture number 36 so let us go to the board so before

I start talking so there are three aspects which I'm going to cover one is the uh an outline of MP and MEP Pathways

and then various isoprenoids and then monotaro and introduction so let us now go to the

what is what are the tarpo so biosynthesis

of tarps so tarps are uh lipid soluble

molecules so they are generally not water soluble and Tarpin noids comprises

of more than 10,000 molecules and they play important role

in the survival of the plant now several or a a significant number of

tarps are important for our uh for our different uses so one important uh area is

essential oil so essential oils are nothing but it's basically a mixture of tarpo components so why we call them

essential oil because basically they have the essence and these are the tar mixture of tarps which are which we

isolate in the form of liquid and they are volatile so volatile tarpo in liquid form having Essence we can call them

essential oil and when they are uh present inside the cell we normally call them as internal pool of

volatiles so that's in general we'll come to that so what how we start is basically that uh we basically talk

about the diversity of different tarpo molecules as I said in the very beginning of the specialized metabolism

class that all the specialized metabolism groups originate from primary metabolism therefore Tarpin noids are

not uh come under any exception so they are very much the upo product of the primary

metabolism so for example I say the three uh atile koi atile qu and this side we

write glycer Al deide three

phosphate plus pyate

so these two joins together and

ultimately contributes to the formation of me

pathway whereas from atile qu M pathway

originates now both these Pathways contributes towards the formation of

isopen pyrophosphate Ip which

are five carbon compounds C5 and this can be converted

into uh dthy alile pyro phosphate that is also

C5 and from here different molecules originate so for

example from dmap joins with one molecule of

Ip and it

forms gpp Jon pyop phosphate and this gpp basically contributes towards the

formation of monot Tarpin monins are C1 so gpp is also

C10 and dma P C5 I IPP C5 so 2 C5 joins and makes C10

uh two more DM joins with two molecules of IPP and

forms fpp which is file p hosit G is there okay and this

again by different reactions contributes towards the

formation of cpin so this is

C15 so say squin s e s q u i t e r p e n e s this is also C15 these are C15

compounds from AP another route

moves towards the formation of squallin s q u a l e n which are C30

compounds andalin ultimately contributes towards the formation of

trins C30 now

dm with three molecules of I i p can

form ggpp Jal gener pyrophosphate which can contribute towards the

formation of D pins it is C20 compound ggpp is

also uh C20 and another

root two molecules of ggpp joins together and contribute towards the formation

of pH toin f phyto are also C40

compounds and phyto in contributes towards the formation of tetr turpins

C40 so this is in brief the origin of different Tarpin from primary metabolize either

through MEP or MV

pathway well so now in the next

slide I will briefly talk about the steps of MEP and MP

pathway so first in brief uh okay in brief only I will cover not in

that details so that is an outline of me

pathway okay first I put first I discuss MPA then I will discuss

M so M originates from two molecules of atile

ko this you should remember and that

makes aceto atile KO and that subsequently

makes HMG qu and then it will

make mevalonic acid so from there the MV now name uh derives the MV stands for

mevalonic acid pathway then it will be mevalonic phosphate then

meet D phosphate then isopentanol D

phosphate or isopen pyop phosphate which we call IP so now let us

join this with arrows so and

the enzymes responsible

are a a aceto acle CO

synthes and then HMG s then

hmgr HMG qu synthes HMG qu reductors thenon Kus then subsequent other enzymes will

not go into that as at the end uh it forms IP so an isopen D phosphate converted into dthy Aly D phosphate that

I will show separately so this is in brief the MV pathway and MV pathway is basically

operating in the cytool that is what you must remember that this this pathway operates in the

cytool whereas now if we talk about the M pathway me

pathway requires joining of leral deide three

phosphate plus pyat pic acid that leads to the formation

of dxp deoxy xylulose phosphate

commonly called dxp and the enzyme is called

dxp synthes and this converted

into map methy edol phosphate

meile D okay let me write the full me c d

okay d for phosphate okay simply

phosphate this will call me me subsequently converted into different

products like cdpm which I'm not going to discuss uh

cdpm then CDP

me then so on and finally it comes to h m

bppp and from here it makes IP P so if I join with

arrows the this is dxr and dxp dioxy Z phosphate reductors

this is called dxr This is called MCT uh then this is called

cmk this is HDR

this is MCS HDs there are so many but we only you only try to

remember dxp synthes or DXs or DXs and dxr because these are the two important and R limiting enzyme here HMG

qu synthes and HMG qu reducted these are the important regulatory enzymes so this you must try to remember and this

pathway is basically operating in the plastid

chloroplast this is the fundamental difference now one more important thing I should tell so may may M pathway was

discovered in late '90s in the microbal system and subsequently it was found in

the plant system only in animal system only in the parasites or protozoa only have the M pathway but not the other

animals and yeah whereas MBA pathway is universal and one interesting point is

this that uh there are several inhibit available to block the NP pathway one of this is

phospho uh fidy so one

antibiotic so that basically inhibits the DXs and this is used in as one of the

alternative antimalarial drug because as I said that me pathway operates only in protozoa so the plasmo

uh the causal organism is a protozoa so giving an inhibitor of M Pathway to block that is basically you are blocking

the metabolism and eventually that will die so that's the beauty now how MEP pathway discovered okay me pathway

discovered from the bacterial point of view there's a different story but from the plant point of view when scientists

they were working on the essential oils production in cell cultures okay

so they were not convinced that it is the MBA pathway which is basically uh modulating the pathway so

feeding the precursors of MBA pathway did not have any effect even blocking the MBA pathway did not have much effect

therefore from that point of time uh a scientist called charl BV charl from Kings College London so he was in of the

opinion that there must be another alternative pathway exist in the plant system which we are not aware of and

much later when MEP pathway uh was described so it was found that MEP pathway significantly

contributes to this tarpine onot tarpine biosynthesis and uh indeed me Pathways contribution is more than MBA

particularly for this monine biosynthesis which is basically operating inside the

plastid okay so that aspect we will come so this is in brief about the uh me and MBA pathway we will not go

into that much detail as I said where detailing is required there we will move okay

now uh let me also give you another overview of this me pathway so uh what are the different products originate

from map pathway that means uh what we can write

diverse products originate

from m so me pathway is also

called it is also called dxp pathway also it's same so you can write in

bracket because dxp was the uh dxp is the first product of the pathway okay and what I said that this

operates in inside the pled okay

okay and if I start with

IP so from this pathway it produces

IP IPP is also produced outside the the plastic by MV pathway so MV pathway which

operates outside the plaster in the citosol also contributes to IPP now there will be cross talk between this

IPP and this IPP that means when there is a shortage of IPP in the plasted then IPP from the produced in the cytool can

move inside and whenever there is a need for more IPP in the cytool the IP produced in the plased can move out so

and as I said along with IP it also produces d m a PP dimethy Al pyrophosphate now dma

PP contributes to different products such

as isoprene irregular tpine

and tar pins also we can see PRS and also this also contributes towards the formation

of cytokinin okay and dmpp from dmpp what we see that gpp is

formed from gpp ggpp is formed okay now gpp

contributes towards the formation of monot Tarpin I'm not happy with this

Arrow so and

ggpp contributes to this the formation of carotenoids and gpp also

contributes towards the formation of phytol and this

phytol takes part in the synthesis of chlorophyll tocoferol

and phyo quos and from

ggpp another root originates leading to the formation of different

bioactive dipin including jar Lin ggp from

gppp through another route it produces plus 2 Quon so this is in

brief different products or diverse products originate from M pathway and uh from

the MV pathway the important products are so anyway because of shortage of space let me put it here

if we put the MV pathway here so the MV pathway

makes IP that into d

m that makes that

makes gpp now this gpp makes fpp Pary pypet and this a plays important role in the synthesis of

cins and trins one it goes to say squ tar pins another

route goes towards the formation of TR turpins trins

and gpp also contributes to ggpp and this

ggpp also contribut to the towards the formation of polypin a good example is rubber so this is basically the major

role played by MBA pathway okay now let us go to the concept

of isoprenoids so isoprenoid are five carbon

molecule so this is the structure of isopen and this is the structure

of isoprene so if you put it in

cch3 double bond ch2

CH double bond ch2 so so ISO prints can make different

configurations for example one is called head to tail [Music]

h this is called head to

tail the other one is called Head to Head no

no get mus this is

called head to head and uh another type which is called

head to Middle this is

called head to Middle okay now let me show you the

example so head to tail the example of such compound is uh

geranial now Head to Head the example is qualin

a b big molecule so here is the point

of head tohe head condensation point and the example of

this is squal in which are C3 compound janal is C 10

compounds okay and the example of head to Middle is I can also

draw which is here so this is the structure

of PIR pyin one so this is also so all these this is

also monine Pine one is monine but it comes under the point of irregular

monot so jonal is monotor squalen is basically

Trine so these are the different ways isoprenoids skeletons

are uh are modified leading to formation of diverse

products uh one more point is this that how this gpp GG gpps are formed so these are

formed by different reactions but uh that may I

may uh discuss in the next class so with this I end this class so let me see what I intend to cover I intend to cover

outline of MV and me pathway this I have covered uh various isoprenoids I have given and monotor in and introduction

very briefly we have not yet started so we'll talk about that in the next class so with this I end this class thank you

very much