13.11.20 Paris

Cysteine synthesis was a key step in the origin of life: study. by University College London.

In an important step during the early evolution of life on Earth, the formation of the amino acid cysteine delivered vital catalysts, which enabled the earliest protein molecules to form in water, according to a new study by UCL researchers.

All proteins are built from the same 20 amino acids. One of these, cysteine, was assumed not to have been present at the origin of life. Despite its fundamental importance to all life today, it was unclear how cysteine might have formed on the early Earth.

In a new study, published in Science, UCL scientists have recreated how cysteine was formed at the origins of life. Additionally, they have observed how, once formed, cysteine catalyses the fusion of peptides in water—a fundamental step in the path towards protein enzymes.

The UCL researchers created cysteine using very simple chemistry and chemicals—hydrogen cyanide and hydrogen sulfide—that were likely to be abundant on the early Earth. The route that they have unravelled closely resembles how cysteine is synthesised in living organisms today, and the researchers believe they are historically linked.

The study also found that cysteine residues catalyse peptide synthesis in water by joining together short peptide fragments that the team had previously found in a study published in Nature last year.

Senior author Professor Matthew Powner (UCL Chemistry) said: "Our results show how cysteine may have formed on the early Earth and how it could have played a critical role in the evolution of protein synthesis.

"Once formed, cysteine catalysts behave as 'proto-enzymes' to produce peptides in water. This robust chemistry could have generated peptides long enough to fold into enzyme-like structures, which would be the precursors to the protein enzymes that are fundamental to all living organisms."

Co-lead author and Research Fellow Dr. Saidul Islam (UCL Chemistry) said: "We have shown that nitriles possess the in-built energy required to form peptide bonds in water. This is the simplest way of making peptides that works with all of the 20 amino acids, which makes it all the more incredible.

"It is precisely the sort of simple, yet special, chemistry that was essential to kick-start life several billion years ago. Our study provides further evidence that the molecules of life descended from nitrile chemistry on the early Earth."

Co-lead author Dr. Callum Foden, who completed the work while a Ph.D. student at UCL, said: "The peptide synthesis we discovered is simple, highly selective and uses molecules that were available on the early Earth.

"A single cysteine residue is enough to produce robust catalytic activity. It is remarkable that such small molecules can carry out such an important (bio)chemical reaction, selectively in water, at neutral pH, and in such high yields."

Discussing further implications of their study, Professor Powner said: "We have resolved a long-standing problem for the origin of life by providing a simple solution to catalytic peptide synthesis in water. Importantly, the catalysts are built only from biology's amino acids. Understanding how cysteine could have controlled the formation of Earth's earliest peptides has made the long path from chemistry to a living organism seem a little shorter, and a little less daunting.

"Our study suggests cysteine was first introduced into life's peptides by modification of serine (another of life's amino acids). This now raises important questions about the early evolution and coding of peptide synthesis. Cysteine is widely assumed not to have been present in life's first genetic code, and this fits neatly with our observations. Our results indicate that encoded serine could furnish cysteine peptides, leading to a key role for cysteine in evolution even before it was assigned to life's genetic code."

Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water:      Science  13 Nov 2020: Vol. 370, Issue 6518, pp. 865-869, DOI: 10.1126/science.abd5680.

View ORCID ProfileCallum S. Foden*, View ORCID ProfileSaidul Islam*, View ORCID ProfileChristian Fernández-García, Leonardo Maugeri, View ORCID ProfileTom D. Sheppard, View ORCID ProfileMatthew W. Powner†

1. ↵†Corresponding author. Email: matthew.powner@ucl.ac.uk

1. ↵* These authors contributed equally to this work.

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Cysteine as peptide precursor and catalyst

Among amino acids, cysteine is highly reactive as a nucleophile, metal ligand, and participant in redox and radical reactions. These properties make cysteine attractive as a component of prebiotic chemistry, but traditional Strecker synthesis of α-aminonitriles, which can serve as peptide precursors, cannot produce free cysteine. Foden et al. found that a simple acylation of the free amine prevented degradation of cysteine nitrile and enabled synthesis of this cysteine precursor from acetyl dehydroalanine nitrile and a sulfide donor (see the Perspective by Muchowska and Moran). When combined with other proteinogenic α-aminonitriles, acetylcysteine or derivative thiols catalyzed efficient peptide ligation in water. These results highlight how prebiotic synthesis of precursors can also generate function by creating a catalyst for polymerization.

Science, this issue p. 865; see also p. 767
Abstract

Peptide biosynthesis is performed by ribosomes and several other classes of enzymes, but a simple chemical synthesis may have created the first peptides at the origins of life. α-Aminonitriles—prebiotic α–amino acid precursors—are generally produced by Strecker reactions. However, cysteine’s aminothiol is incompatible with nitriles. Consequently, cysteine nitrile is not stable, and cysteine has been proposed to be a product of evolution, not prebiotic chemistry. We now report a high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic pathway converts serine to cysteine by nitrile-activated dehydroalanine synthesis. We also demonstrate that N-acylcysteines catalyze peptide ligation, directly coupling kinetically stable—but energy-rich—α-amidonitriles to proteinogenic amines. This rare example of selective and efficient organocatalysis in water implicates cysteine as both catalyst and precursor in prebiotic peptide synthesis.

11.3.20 Tanger

La perméabilité des liposomes, p. 317 296 et les pores dans la phase cubique, p. 281, revew 2015

Le métabolisme prébiotique et l'overcrowding: p 396

Construire à partir du toit: p.55

fischer-tropsch: p. 51

La logique de l'organisation interne, p.155

• p.168    (1er paragraphe) pour la cognition ( en arabe معرفة , prendre connaissance), ** the interaction with the environment -- actually the "perturbation" -- in order to be accepted, must be consistent with the internal logic of the living. In order words, the interaction between an autopoietic unit and a given molecule X is not primarily dictaded by the properties of the molecule X, but by the way in wich this molecule is "seen" by the living organism. **
  
• p.167  (paragraphe 5) le point de vue de Luisi, différent de Maturana et Varela, ** recognizing namely that the bringing forth of a world (faire naître un monde, forth, apporter un monde en avant) is due to the cognitive interaction of the living with the environment, and that this interaction can be linked to the biochemistry of the living organism.**
• Sans parler de métabolisme et surtout sans aucune réaction covalente, comme au début des PEEMOVs, l'interaction entre l'être vivant et l'environnement est de nature quantique: l'état vibratoire de la molécule X interfère avec l'état vibratoire de l'être vivant ou du liposome en cours d'auto-organisation. La logique du liposome naissant n'a pas à accepter ou refuser la molécule X, mais réagit en l'incorporant, parce qu'elle entre en résonance avec le liposome (la logique du liposome) soit en l'expulsant parce que l'état vibratoire du liposome le permet. Du point de vue de la molécule X, s'il n'y a pas résonance, son état vibratoire pourrait être si fort qu'il détruirait l'organisation du liposome. Par exemple pour le début de l'origine de la vie, avant les réactions covalentes, les ions beryllium  désorganiseraient le liposome en se mettant à la place des ions calcium.

22.09.14 Paris transféré dans Duve-2005 sur mon disque

23.09.14

23.06.2013

A partir de KEGG recherche d'une protéine membranaire (par exemple transport (others), énergie, PLD ...), puis recherche de ECO (E.Coli) et à droite cliquer sur Uniprot puis choisir "Original site". En plus de cequi est affiché cliquer sur détails de la structure secondaire pour avoir la partie hélice des zones périplasmiques et cytoplasmiques.

KEGG transporters

Aquaporin Z:  231 aas   6 hélices membranaires et 13 en structure secondaire

Voltage-gated potassium channel Kch : 417 aas 6 hélices membranaires et 8 en structure secondaire

Ammonia channel amtB : 428 aas 11 hélices membranaires et 23 en structure secondaire (pls de + de 30 aas)

Potassium efflux system KefA : 1120 aas 11 hélices membranaires pas de structure secondaire

Outer membrane protein F ompF : 362 aas que des béta membranaires (17) et 3 hélices en secondaires le reste en béta. 

Magnesium transport protein CorA : 316 aas 2 hélices membranaires pas de structure secondaire

Zinc transport protein ZntB : 327 aas 2 hélices membranaires pas de structure secondaire

Sodium/proline symporter : 502 aas 12 hélices membranaires pas de structure secondaire

GABA permease gabP : 466 aas 12 hélices membranaires pas de structure secondaire

Na(+)/H(+) antiporter subunit A mrpA : 805 aas 21 hélices membranaires pas de structure secondaire    Bacillus pseudofirmus (strain OF4)

Phosphate transport system permease protein PstC : 319 aas 6 hélices membranaires pas de structure secondaire

Phosphate-binding protein PstS : 346 aas periplasme. Structure secondaire avec 13 hélices et 12 béta

Phosphate import ATP-binding protein PstB : 257 aas membranaire. Pas de structure secondaire mais ATP binding.

Phosphate transport system permease protein PstA : 296 aas 6 hélices membranaires pas de structure secondaire

KEGG Phospholipides

CDP-diacylglycerol pyrophosphatase cdh  EC.3.6.1.26: 251 aas 1 hélice membranaire pas de structure secondaire

CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase EC 2.7.8.5 :  182 aas 4 hélices membranaires pas de structure secondaire

Phosphatidate cytidylyltransferase EC 2.7.7.41 :  285 aas 8 hélices membranaires pas de structure secondaire

21.06.2013

Phosphorylation oxydative KEGG

ATP synthase subunit c : 79 aas 2 hélices membranaires et 2 en structure secondaire

ATP synthase subunit a : 271 aas 5 hélices membranaires et 4 en structure secondaire

Succinate dehydrogenase cytochrome b556 subunit sdhC : 129 aas 3 hélices membranaires et 5 en structure secondaire

Succinate dehydrogenase cytochrome b556 subunit sdhD : 115 aas 3 hélices membranaires et 4 en structure secondaire

C'est un livre open access: Reviews in Mineralogy & Geochemistry volume 75, 2013.