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Intelligent Design, the best explanation of Origins » Origin of life » Amazing molecular assembly lines and non ribosomal amino-acid chain formation pathways come to light

Amazing molecular assembly lines and non ribosomal amino-acid chain formation pathways come to light

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Amazing molecular assembly lines and non-ribosomal amino-acid chain formation pathways come to light

http://reasonandscience.heavenforum.org/t2445-new-amazing-molecular-assembly-lines-and-non-ribosomal-amino-acid-chain-formation-pathways-come-to-light

If you thought there is only one way to make polypeptide amino-acid chains by the well-known process  DNA => RNA polymerase => mRNA => Ribosome + tRNA =>>  amino-acid polypeptides, you did not hear  until now ( as me ) ut NRPS, or Nonribosomal peptide synthetases. Well, you might ask, how do they work and what do they produce? Maybe I should start and explain first, how I came to know about them. The best way to learn about molecular biology is to get curious, ask questions, and dig deep,  until reach the bottom. Follow the evidence like Sherlock Holmes.

I was starting to read the book A privileged Planet, and at page 201,  Gonzales writes: The strong nuclear force is responsible for holding protons and neutrons together in the nuclei of atoms. In such close quarters, it is strong enough to overcome the electromagnetic force and bind the otherwise repulsive, positively charged protons together. It is as short-range as it is strong, extending no farther than atomic nuclei. But despite its short range, changing the strong nuclear force would have many wide-ranging consequences, most of them detrimental to life.  The periodic table of the elements would look different with a changed strong nuclear force. If it were weaker, there would be fewer stable chemical elements. The more complex organisms require about twenty-seven chemical elements, iodine being the heaviest (with an atomic number of 53). Instead of ninety-two naturally occurring elements, a universe with a strong force weaker by 50 percent would have contained only about twenty to thirty. This would eliminate the life-essential elements iron and molybdenum. 

Molybdenum, life essential? Hmm, yes, of course. I read about Molybdenum required in nitrogenase enzymes in cyanobacteria. So my next question was: What are the life-essential elements for life? Here the list:

Essential elements and building blocks for the origin of life
http://reasonandscience.heavenforum.org/t2437-essential-elements-and-building-blocks-for-the-origin-of-life

So, I went on and gave a closer attention to Molybdenum.  I remembered that the amazing nitrogenase enzyme which works like a molecular sledge-hammer, breaks the molecular triple bond of nitrogen, and transforms nitrogen gas into ammonia, essential for the makeup of living things, and it uses in its active site as co-factor molybdenum.

The Nitrogenase enzyme,  the molecular sledgehammer  
With assistance from an energy source (ATP) and a powerful and specific complementary reducing agent (ferredoxin), nitrogen molecules are bound and cleaved with surgical precision. In this way, a ‘molecular sledgehammer’ is applied to the NN bond, and a single nitrogen molecule yields two molecules of ammonia. The ammonia then ascends the ‘food chain’, and is used as amino groups in protein synthesis for plants and animals. This is a very tiny mechanism, but multiplied on a large scale it is of critical importance in allowing plant growth and food production on our planet to continue.
http://reasonandscience.heavenforum.org/t1585-nitrogenase#2406

So my next question was: How are the MOLYBDENUM COFACTORs synthesized, the essential active sites for nitrogenase function that contain molybdenum ?

So this lead me to following research:

Molybdenum, essential for life
http://reasonandscience.heavenforum.org/t2430-molybdenum-essential-for-life

So i discovered, that for the starting point of molybdenum co-factor maturation ( or biosynthesis ), Iron-Sulfur ( FE/S) clusters  are used. They were not unknowns to me. I studied about them some time ago:

Biosynthesis of Iron-sulfur clusters, basic building blocks for life  
http://reasonandscience.heavenforum.org/t2285-iron-sulfur-clusters-basic-building-blocks-for-life

So, i asked myself: In order to make FE/S clusters, the cell needs the uptake of Iron and Sulfur. How does that happen in the cell ? Here we go:

Sulfur essential for life
http://reasonandscience.heavenforum.org/t2433-sulfur-essential-for-life

Iron Uptake and Homeostasis in Cells
http://reasonandscience.heavenforum.org/t2443-iron-uptake-and-homeostasis-in-prokaryotic-microorganisms

And here comes the amazing part: 

Iron Bioavailability
Although iron is one of the most abundant elements on Earth, the environment is usually oxygenated, non-acidic, and aqueous. Under these conditions, extracellular iron is predominantly found in the poorly soluble ferric (Fe3+) state. One way that organisms such as yeast improve iron bioavailability is by acidifying the local environment.  By lowering the pH of the surrounding environment, organisms facilitate solubilization and uptake of iron. ATP-driven proton transporters move H+ ions from the cytosol across the plasma membrane to control the pH at the cell surface.

Question: Had this system not have to emerge fully setup right from the beginning in order to facilitate and make Iron uptake into the cell even possible ?

Uptake of Iron by micro-organisms like Bacteria and fungi
Many microorganisms, including some fungi, also secrete low molecular weight compounds known as siderophores into their surroundings, which form high-affinity (~10−33 M) complexes with ferric iron to make it bioavailable for uptake. Transporters on the cell surface then recapture the Fe3+-siderophores complexes.  

Wow... now comes the most fascinating part. To make these siderophores, incredible assembly lines in the cell are used: 

Its remarkable, how Nature magazine describes in the article Enzymes line up for assembly ,  how non-ribosomal peptide synthetase (NRPS) work ( we are back at the starting point of this article ) :

Nearly 100 years ago, Henry Ford demonstrated the full strength of economist Adam Smith’s insights into productivity and the division of labour when he established the first moving assembly line. By shuttling partially constructed cars mechanically from one worker to the next, each performing a single specific task, Ford’s assembly line could issue a new Model T every three minutes. This manufacturing method provided the foundation of modern mass production. But nature employed much the same approach for constructing molecules long before humans existed to ponder questions of economy and efficiency.  Walsh and colleagues  identify a previously unrecognized link in one such biological assembly line — an enzyme that could some day be exploited by chemists to modify complex, naturally occurring compounds. The enzymes that form the polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) families are responsible for the biosynthesis of many useful compounds, including the antibiotics erythromycin and vancomycin, and the antitumour drug epothilone. These multi-subunit enzymes are the molecular equivalents of moving assembly lines: growing substrate molecules are handed, bucket-brigade style, from one specialized catalytic site to the next, with each site performing a specific and predictable function. The PKS assembly line starts by recruiting The PKS assembly line starts by recruiting small building-blocks (such as acetate and propionate molecules, which contain ‘acyl’ chemical groups) onto carrier proteins. The building-blocks are then bonded together in reactions catalysed by a ‘ketosynthase’ region of the PKS. The resulting substrate may then be chemically tailored by various other enzyme domains, before being passed on to another ketosynthase for a further round of extension and modification. The cycle is repeated until the finished molecule is finally offloaded. The various catalytic domains may exist as discrete enzymes (as in type II PKS), or be connected end to end, like beads on a string (as in type I PKS), but in both cases the biosynthetic strategy remains the same. The NRPS cycle is very similar to that of PKS enzymes, except that it uses amino acids as building-blocks. Thus, amino acids become bound to peptidyl carrier proteins (PCPs); PCP-bound amino acids are joined together with amide bonds to form peptides, in catalytic sites known as condensation domains; tailoring regions may then modify the newly formed peptide before passing it along for further cycles of extension and tailoring; and finally, the finished product is cleaved from the enzyme. The PKS and NRPS enzymes each produce very different products, but the logic they use is strikingly similar — so similar, in fact, that they can easily cooperate to construct hybrid PKS–NRPS products such as epothilone.





this assembly line, together with non-ribosomal codes, produces siderophores, essential for the uptake of iron in bacterias. Iron, essential for the synthesis of FE/S clusters. FE/S clusters, essential for the formation of Molybdenum cofactors.  All above-described cell processes must exist prior life began, in order to produce Molybden co-factors, essential for various life-essential processes.

Minerals containing molybdenum are key in assembling atoms into life-forming molecules. The researcher points out that boron minerals help carbohydrate rings to form from pre-biotic chemicals, and then molybdenum takes that intermediate molecule and rearranges it to form ribose, and hence RNA. Chromium, molybdenum, selenium, and vanadium, for example, are essential for building proteins, and proteins serve as life’s molecular “factories.”

The scientific evidence exposed points to the requirement of 1. finely tuned fundamental forces to make the higher elements, like Molybden 2. Molecular assembly lines and biosynthesis pathways fully setup right from the beginning, 3. Interdependence and irreducible processes all along inside the cell, and all these processes had to emerge all at once, intelligently created, fully set up,  with an initial injection of instructional complex information.  A cell membrane to host siderophores, ABC transporters, membrane proteins for the sensing and intake of the substrates,  mechanisms for homeostasis control etc. if you have an automobile, and you lose the key to turn it on, it will not function. What was the key for the event of the moment of transition from non-life to life? All cellular compartments, essential proteins, and molecular machines, replication process and mechanism, habilitiy of sensing and recognition of the environment, organization, information, regulation, nutrition uptake, cell wall, metabolism had to be there, or there would not be the first go. If just a tiny part of the machinery to make siderophores for uptake of iron was not there, no iron would have been disposed to the cell, no FE/S cluster formation, no Molybden cluster formation, no proteins that use it in their active site could emerge, no life....just a tiny part missing, no life. How could someone with even a superficial understanding of how life and cells work, argue that chemical evolution and stepwise, down up process could produce life?A stepwise, gradual origin of these processes is impossible and would equal to a miracle. 



Last edited by Admin on Sun Feb 11, 2018 7:14 am; edited 3 times in total

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Another Code system in the cell comes to light:

Calcium signaling is one of the most extensively employed signal transduction mechanisms in life. 10 Calcium ions (Ca2+) serve as a universal signal to modulate almost every aspect of cellular function in all cells. Calcium carries messages to virtually all important functions of cells. Ca2+ signaling pathway plays a key second messenger role in regulating many cellular processes in virtually all types of animal cells including fertilization, contraction, exocytosis, transcription, apoptosis, and learning and memory.

Beside the 10 code systems in the cell i cataloged already:

http://reasonandscience.heavenforum.org/t2213-the-various-codes-in-the-cell

namely :

The Genetic Code
The Splicing Codes
The Metabolic Code
The Signal Transduction Codes
The Signal Integration Codes
The Histone Code
The Tubulin Code
The Sugar Code
The Glycomic Code
The non-ribosomal code

we can add the

The Calcium signal code:

Combining Genetics and Cell Biology to Crack
the Code of Plant Cell Calcium Signaling
http://labs.biology.ucsd.edu/schroeder/pdfs/STKE_allen_and_schroeder.pdf

The Calcium Code
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1225038/?page=1

Another outstanding implication of the existence of organic codes in Nature comes from the fact that any code involves meaning and we need therefore to introduce in biology, with the standard methods of science, not only the concept of biological information but also that of biological meaning. The study on the organic codes, in conclusion, is bringing to light new mechanisms that operated in the history of life and new fundamental concepts. It is an entirely new field of research, the exploration of a vast and still largely unexplored dimension of the living world, the real new frontier of biology.

The Algorithmic Origins of Life
If life is more than just complex chemistry, its unique informational management properties may be the crucial indicator of this distinction, which raises the all-important question of how the informational properties characteristic of living systems arose in the first place. This key question of origin may be satisfactorily answered only by first having a clear notion of what is meant by “biological information”. Unfortunately, the way that information operates in biology is not easily characterized. While standard information-theoretic
measures, such as Shannon information, have proved useful, biological information has an additional quality which may roughly be called “functionality” – or “contextuality” – that sets it apart from a collection of mere bits as characterized by Shannon Information content. Biological information shares some common ground with the philosophical notion of semantic information (which is more commonly – and rigorously – applied in the arena of “high-level” phenomena such as language, perception and cognition).We therefore identify the transition from non-life to life with a fundamental shift in the causal structure of the system, specifically, a transition to a state in which algorithmic information gains direct, context-dependent, causal efficacy over matter.
http://arxiv.org/pdf/1207.4803v2.pdf

Wanna Build a Cell? A DVD Player Might Be Easier

http://reasonandscience.heavenforum.org/t2404-wanna-build-a-cell-a-dvd-player-might-be-easier

communication, by definition, requires four things to exist:

1. A code
2. An encoder that obeys the rules of a code
3. A message that obeys the rules of the code
4. A decoder that obeys the rules of the code

These four things—language, transmitter of language, message, and receiver of language—all have to be precisely defined in advance before any form of communication can be possible at all.

Coded information comes always from a mind
http://reasonandscience.heavenforum.org/t1312-coded-information-comes-always-from-a-mind

Role of Calcium Ions in the Cell and Bacterial Calcium Metabolism
http://reasonandscience.heavenforum.org/t2448-role-of-calcium-ions-in-the-cell-and-bacterial-calcium-metabolism

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Siderophores 

Under iron-limited conditions, many Gram-negative and Gram-positive bacteria synthesize low molecular weight iron-chelating compounds known as siderophores. The role of these compounds is to scavenge iron from precipitates or host proteins in the microorganism's extracellular milieu. Currently, there are almost 500 compounds that have been identified as siderophores. Although siderophores differ widely in their overall structure, the chemical natures of the functional groups that coordinate the iron atom are not so diverse. Siderophores incorporate either α-hydroxycarboxylic acid, catechol, or hydroxamic acid moieties into their metal binding sites and thus can be classified as either hydroxycarboxylate, catecholate, or hydroxamate type siderophores. Of all of the bacterial iron uptake pathways, the pathway for the uptake of ferric siderophores is the most structurally well defined.

Siderophores are small ligands of 500–1500 Da that exhibit a high affinity for Fe3+.Siderophores are produced by a wide range of organisms (bacteria, fungi, diatoms, graminaceous plants) in all sorts of environments (terrestrial, soil, freshwater, open ocean, coastal ocean water) with more than 500 siderophores identified. Most siderophores are synthesized by nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs) with chemical structures classified as catechol, hydroxamate, or alpha-hydroxycarboxylate. Siderophores chelate the relatively insoluble Fe3+, which enables organisms with adequate siderophore uptake systems to import this oxidized form of iron. Organisms can produce one or several siderophores, along with the corresponding uptake systems, but organisms can also scavenge siderophores that are produced by other species (in this case siderophores that are scavenged from another species are called xenosiderophores). In Gram-negative bacteria, the typical siderophore uptake system consists of an outer membrane ferrisiderophore receptor that interacts with a siderophore-specific TonB-ExbB-ExbD complex to provide the energy for translocation of the siderophore into the periplasm. Once in the periplasm, an ABC transporter cassette, comprised of a periplasmic siderophore-binding protein, permease, and ATPase, then imports the ferrisiderophore into the cytoplasm.

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Iron mobilization and uptake - an essential process in all domains of life

Maintaining adequate intracellular levels of transition metals is fundamental to the survival of ALL organisms. While all transition metals are toxic at elevated intracellular concentrations, metals such as iron, zinc, copper, and manganese are ESSENTIAL to many cellular functions. In prokaryotes, the CONCERTED action of a battery of membrane-embedded transport proteins controls a delicate balance between sufficient acquisition and overload.

My comment: There is no energy gradient between the inside and outside of the cell, where Iron is naturally attracted or " sucked" into the cell. So there is no "natural" reason for Iron to move from the outside into the inside of the cell. Iron, furthermore, needs to be " chelated", or bound to so-called siderophores, in order to be transported into the cell. This is orchestrated by a complex ATP and membrane-bound enzyme-mediated process.  

Many microorganisms, including some fungi, also secrete low molecular weight compounds known as siderophores into their surroundings, which form high-affinity (~10−33 M) complexes with ferric iron to make it bioavailable for uptake. Transporters on the cell surface then recapture the Fe3+-siderophores complexes.

Siderophores are made literally by molecular assembly lines through so-called  non-ribosomal peptide synthetase (NRPS)

http://reasonandscience.heavenforum.org/t2445-amazing-molecular-assembly-lines-and-non-ribosomal-amino-acid-chain-formation-pathways-come-to-light

Nature magazine reports:
Nearly 100 years ago, Henry Ford demonstrated the full strength of economist Adam Smith’s insights into productivity and the division of labor when he established the first moving assembly line. By shuttling partially constructed cars mechanically from one worker to the next, each performing a single specific task, Ford’s assembly line could issue a new Model T every three minutes. This manufacturing method provided the foundation of modern mass production. But nature employed much the same approach for constructing molecules long before humans existed to ponder questions of economy and efficiency.  Walsh and colleagues identify a previously unrecognized link in one such biological assembly line — an enzyme that could someday be exploited by chemists to modify complex, naturally occurring compounds. The enzymes that form the polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) families are responsible for the biosynthesis of many useful compounds

These multi-subunit enzymes are the molecular equivalents of moving assembly lines: growing substrate molecules are handed, bucket-brigade style, from one specialized catalytic site to the next, with each site performing a specific and predictable function. The PKS assembly line starts by recruiting The PKS assembly line starts by recruiting small building-blocks (such as acetate and propionate molecules, which contain ‘acyl’ chemical groups) onto carrier proteins. The building blocks are then bonded together in reactions catalyzed by a ‘ketosynthase’ region of the PKS. The resulting substrate may then be chemically tailored by various other enzyme domains, before being passed on to another ketosynthase for a further round of extension and modification. The cycle is repeated until the finished molecule is finally offloaded. The various catalytic domains may exist as discrete enzymes (as in type II PKS), or be connected end to end, like beads on a string (as in type I PKS), but in both cases the biosynthetic strategy remains the same. The NRPS cycle is very similar to that of PKS enzymes, except that it uses amino acids as building-blocks. Thus, amino acids become bound to peptidyl carrier proteins (PCPs); PCP-bound amino acids are joined together with amide bonds to form peptides, in catalytic sites known as condensation domains; tailoring regions may then modify the newly formed peptide before passing it along for further cycles of extension and tailoring; and finally, the finished product is cleaved from the enzyme. The PKS and NRPS enzymes each produce very different products, but the logic they use is strikingly similar — so similar, in fact, that they can easily cooperate to construct hybrid PKS–NRPS products such as epothilone.

This amazing molecular assembly line, together with non-ribosomal codes, produces siderophores, essential for the uptake of iron in bacterias.

Once these siderophores are synthesized, they bind or chelate Iron, and the process of Iron uptake and transport inside the cell can begin.

It is estimated that 30–45% of known enzymes are metalloproteins that depend on a metal co-factor for their function.  Often, the co-factor is a transition metal such as iron, manganese, zinc, or copper. As a result, many essential physiological processes including respiration, photosynthesis, replication, transcription, translation, signal transduction, and cell division depend on the presence of transition metals. However, transition metals are toxic at elevated intracellular concentrations as they can perturb the cellular redox potential, produce highly reactive hydroxyl radicals, and displace functionally important metal co-factors from their physiological locations.

In both eukaryotes and prokaryotes, a diverse ensemble of membrane-embedded transporters participates in metal translocation across cell membranes.

ABC transporters are embedded in the inner membrane, and through interactions with their cognate substrate-binding proteins, outer membrane receptors , and the ExbB/ExbD/TonB system they participate in metal uptake through the outer membrane, the periplasm, and the inner membrane, delivering transition metals to the cytoplasm. Following protein complexes are INDISPENSABLE:

Outer membrane transporters (TBDT)
ExbB/ExbD/TonB system
ATP-binding cassette (ABC) transporter
Periplasmic binding protein (PBP)

are required for Iron (Fe), Vitamin B12, and other transition metal uptake, while

RND
P-type ATPase
CDF

are used to expel overload of B12 and transition metals.

The scientific evidence exposed points to the requirement of 1. finely tuned fundamental forces to make the higher elements, like Molybden 2. Molecular assembly lines and biosynthesis pathways fully setup right from the beginning, 3. Interdependence and irreducible processes all along inside the cell, and all these processes had to emerge all at once, intelligently created, fully set up,  with an initial injection of instructional complex information.  A cell membrane to host siderophores, ABC transporters, membrane proteins for the sensing and intake of the substrates,  mechanisms for homeostasis control etc. if you have an automobile, and you lose the key to turn it on, it will not function. What was the key for the event of the moment of transition from non-life to life? All cellular compartments, essential proteins, and molecular machines, replication process and mechanism, the ability of sensing and recognition of the environment, organization, information, regulation, nutrition uptake, cell wall, metabolism had to be there, or there would not be the first go. If just a tiny part of the machinery to make siderophores for uptake of iron was not there, no iron would have been disposed to the cell, no FE/S cluster formation, no Molybden cluster formation, no proteins that use it in their active site could emerge, no life....just a tiny part missing, no life. How could someone with even a superficial understanding of how life and cells work, argue that chemical evolution and stepwise, down up process could produce life?A stepwise, gradual origin of these processes is impossible and would equal to a miracle.

More:
Biosynthesis of the Cofactors of Nitrogenase  
http://reasonandscience.heavenforum.org/t2429-biosynthesis-of-the-cofactors-of-nitrogenase

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Siderophore production and secretion occurs, especially under iron starvation, when the intracellular iron concentration drops under a certain threshold required for functionality. Depending on the chemical nature of the organic ligand that coordinates iron, siderophores can be divided into three main classes,

the catecholates,
the hydroxamates or mixed-types that contain another iron complexing group such as α-hydroxy-carboxylate next to
the hydroxamate or catecholate group.

Once bound to Fe(III), the ferrisiderophore is transported back into the host cell via specific transporters on the cell surface. The hydroxamate-type siderophore schizokinen is a derivative of citric acid and chelates iron via two α-hydroxamate groups and one α-hydroxy-carboxylate group. The function of schizokinen is thought to be twofold. On the one hand, it is part of the iron acquisition strategy and on the other hand, schizokinen – as well as other siderophores – is able to complex copper. This activity was found to be required for alleviating copper toxicity. 


Siderophore Synthesis
At least three different systems are involved in siderophore synthesis in cyanobacteria; two of them belonging to the non-ribosomal peptide synthetases (NRPSs), which catalyse the peptide bonds between amino acid monomers of the siderophore backbone. The core module of an NRPS consists of three domains: the adenylation (A) domain for activation of the selected amino acid monomer, a peptidyl carrier domain (P) for transferring the monomers to various catalytic sites and a condensation (C) domain for forming peptide bonds between the monomers

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