**2. Early chemodiversity was non-biotic**

#### **2.1. From single elements to simple organic molecules in a mineral world**

Chemistry is as ancient as the observable universe, ca. 13.7 billion years old according to present estimates. The simplest elements of the periodic table (namely, hydrogen, helium and traces of lithium) were formed as an immediate consequence of the Big Bang.

The *nuclear chemistry* of the galaxies and stars which developed during the following few billion years is the chemistry of very high energies, yielding a small and finite number of chemical species, some very short-lived. Carbon, oxygen and nitrogen came to existence. The data on star-forming elements is of spectroscopic nature. When decomposed and analyzed, the light emitted by these objects reveals the presence of spectral lines at set wavelengths, and their association forms fingerprints typical of individual elements when heated to incandescence. The solar system was formed about 4.6 billion years ago by the accretion of *simple molecular substances* from a giant cloud at the center of which most the concentrating matter formed the sun, the rest forming a disc from which primary planets, then satellites planets emerged under various scenarios.

Under very hot temperatures and no atmosphere, the molecular chemistry associated with proto-planets is dominated by inorganic entities, with very limited diversity in carbon chemistry. Carbon dioxide and water probably existed as soon as oxygen, a stellar product, had been available to combine with hydrogen, yet early planet Earth was most likely very hot and dry, precluding life and any of the complex chemistries it produces. This characterized the Hadean, the first geologic eon (4.6 to 4.0 billion years until conflicting evidences such as the presence of high d18O (oxygen isotopic ratios) in zircons tentatively dated as early as 4.4 billion years led to a reassessment of the transition between the "molten" planet (and formation of the moon) and the "solid" planet with a solid crust, a low temperature, and an atmosphere of sorts, and the possible presence of liquid water. As well as this "cool early earth" hypothesis [1], a partial explanation about the formation of oceans is that asteroids and perhaps comets carrying huge amounts of ice collided with our planet, adding to the putative *de novo* conden‐ sation into water during the degassing of rocks of the cooling planet. In the primitive atmos‐ phere, heavier carbon dioxide became partly quenched by dissolving in oceanic waters, and partly trapped under plate tectonic movements.

#### **2.2. The chemical origin of life on earth — Chemodiversity goes organic**

Any life form necessitates the capacity to harvest energy for its own benefit, to manage chemical reactions within molecular boundaries that define it as an entity distinct from the environment, i.e. *self* vs. *non-self*, and to have the potential to replicate itself.

Irrespective of when the right conditions were first met for life to emerge, a small set of small organic molecules (reactants) is a prerequisite for the abiotic generation of life-essential molecules, in the presence of water and of some catalytic trigger, and later of thermodynam‐ ically favorable conditions for polymers to be built.

Different approaches have attempted to address the question of the chemical origin of life, leading to apparently conflicting conclusions: the "prebiotic soup theory" and the "pioneer organism theory", fueling heated debate among specialists, and also reflecting the uncertainties that still remain on the greatest mystery in science. The following paragraph attempts to follow the most generally accepted views and the most plausible scenario.

#### *2.2.1. The Miller-Urey laboratory experiments*

Over the last three decades, warning messages have been sent to the community about the destructive consequences worldwide economic development will have on biodiversity, both terrestrial and marine, during the 21st century. Direct impacts are caused by overexploitation and mismanagement of natural resources and improper recycling and disposal of waste products. Indirect impacts are caused by the accelerating volatilization of greenhouse mole‐ cules and their accumulation in the atmosphere where they may undergo undesirable speciation. Restitution of sulfur emissions to land may cause acidic rains and transfer of carboncontaining emissions to seawater increases its acidity, both leading to biodiversity destructive scenarios. Not to mention the release of man-made (synthetic) molecules, some of which like CFCs destroy the anti-UV ozone shield, others like PCBs accumulating along food chains and eventually killing top consumers. Synthetic molecules may respond to specific needs and criteria, but they will never replace natural molecules, in the same way as genetically trans‐ formed organisms will never replace wildlife diversity. Moreover, freak biological or chemical species should be eliminated safely once the purpose for which they were created has been

To-date, very little is said or written on the fate of natural chemodiversity within the context of local or general biodiversity collapse, both terrestrial and marine. After a brief historical account of the intricate connections between chemodiversity and biodiversity since life appeared on our planet, this chapter attempts to demonstrate that natural molecular diversity

Chemistry is as ancient as the observable universe, ca. 13.7 billion years old according to present estimates. The simplest elements of the periodic table (namely, hydrogen, helium and

The *nuclear chemistry* of the galaxies and stars which developed during the following few billion years is the chemistry of very high energies, yielding a small and finite number of chemical species, some very short-lived. Carbon, oxygen and nitrogen came to existence. The data on star-forming elements is of spectroscopic nature. When decomposed and analyzed, the light emitted by these objects reveals the presence of spectral lines at set wavelengths, and their association forms fingerprints typical of individual elements when heated to incandescence. The solar system was formed about 4.6 billion years ago by the accretion of *simple molecular substances* from a giant cloud at the center of which most the concentrating matter formed the sun, the rest forming a disc from which primary planets, then satellites planets emerged under

Under very hot temperatures and no atmosphere, the molecular chemistry associated with proto-planets is dominated by inorganic entities, with very limited diversity in carbon chemistry. Carbon dioxide and water probably existed as soon as oxygen, a stellar product,

is a treasure to preserve for future generations, using a series of marine examples.

**2.1. From single elements to simple organic molecules in a mineral world**

traces of lithium) were formed as an immediate consequence of the Big Bang.

**2. Early chemodiversity was non-biotic**

fulfilled.

70 Biodiversity - The Dynamic Balance of the Planet

various scenarios.

The prebiotic soup theory stems from the early experiments of Stanly Miller and Harold Urey [2] which led to the condensation within days of a suite of five amino acids by exposing a sterile mixture of methane (CH4), ammonia (NH3), carbon monoxide (CO) and hydrogen (H2) - i.e. the "primitive gases", to a constant flux of hot water (H2O), while discharging electric sparks (to simulate thunder) into the gas mixture. New species such as hydrogen cyanide (HCN), formaldehyde (HCHO) and reactive intermediates (acetylene, cyanoacetylene etc.) are formed in one-step, while amino acids and other biomolecules are formed from these reactants under reducing conditions (Fig. 1), i.e. the Strecker synthesis.

Some 50 years later, Bada and collaborators (in [3]) reanalyzed archived samples of Stanly Miller's experiments in which the gaseous mixture included hydrogen sulphide (H2S), methane (CH4), ammonia (NH3), and carbon dioxide (CO2). In the case of this experiment (unreported by Miller at the time), no less than 27 compounds, including the 20 "regular" amino acids and 3 new ones were found. Specifically, the presence of hydrogen sulphide and carbon dioxide as reactants - originally proposed to simulate the influence of volcanic emissions - had enriched the diversity of the reaction products with seven several sulphur-containing com‐ pounds, including methionine and cysteine), and four amines as well.

*2.2.3. Transposing to "real" prebiotic conditions*

complexes.

scenario.

is another story.

interest.

*2.2.4. Before and during the RNA world*

In order to transpose from lab experiments to real life situation, several criteria must be met in order to initiate amino acid synthesis: the reactants must be concentrated enough under an

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The primitive soup theory relies on a stochastic occurrence of optimal conditions for the emergence of organic life. Polymerization necessitates suitable absorbing substrates and catalysts such as metal cations and imidazole derivatives and several others, to proceed in laboratory conditions. Charged submicronic montmorillonite clay particles would have helped activated monomers to selectively concentrate (electrostatic bonds) and induce covalent polymerization. Shallow lagoons in tidal zones may theoretically provide basic chemistry. Evaporation induces concentration and promotes the formation of eutectic

Contenders of the "primitive soup" scenario advocate that life may have arisen through chemoautotrophic processes occurring in oceanic depths in the vicinity of hydrothermal settings which would provide all necessary starting conditions [7]. In this "pioneer metabo‐ lism" scenario, the generation of homochiral metalloenzymes of extant organisms from inorganic transition metal precipitates (by chelation of alpha-hydroxyl and alpha-amino acids ligands) follows a stepwise evolution by autocatalytic feedback. This "hot volcanic" prebiotic chemistry is often opposed to the "cool oceanic" chemistry that typifies the primitive soup

It appears that the composition of the primitive atmosphere is not what it was thought to be at the time of Miller's experiments, certainly not as reducing, and the conditions afforded in the hydrothermal vent environments appear more amenable to prebiotic chemistry. Oligomers

However, prebiotic chemistry under early atmospheric conditions has opened the issue towards exobiology. Scientists of repute now speculate on an extraterrestrial origin of life, or at least in the alien seeding of life essential molecular building blocks on planet earth. But this

The recent finding that ribonucleic acids (RNAs) can perform a variety of hitherto unsuspected structural and metabolic functions in cells has given credit to Walter Gilbert's prediction [9] that an all-RNA world had preceded the nucleic acid-protein world as we know it today. The fact that RNA takes evolutionary precedence on DNA (itself regarded by some as a modified RNA better suited for the conservation of genetic information), or the fact that RNAs as a catalysts (ribozymes) take precedence on enzyme catalysts, stimulate intense experimental

Nucleotide monomers can theoretically be surface-assembled as oligomers [10]. The longest strands serving as templates, direct synthesis of a complementary strand starting from monomers or short oligomers, and double-stranded RNA molecules can accumulate. Disso‐

could have then been formed at liquid-solid interfaces [8].

aqueous environment under favorable temperature and pH conditions.

**Figure 1.** The apparatus used by Miller and Urey in their 1953 simulated early-earth experiment on the chemical ori‐ gins of life. In the original experiment, the gases of the primitive atmosphere were: NH3, CH4, H2 and water vapor. Oth‐ er experiments were carried out under non-reducing conditions (using CO2, N2 and water) and UV exposure led to poor yields. In experiments simulating volcanic environments, Miller and Urey used H2S, CH4, NH3 and CO2 (see text). (Graphics by Yassine Mrabet in http://en.wikipedia.org/wiki/Miller-urey\_experiment)

#### *2.2.2. Other "prebiotic" laboratory experiments*

Oró and collaborators [4] using similar experimental setups, established that adenine and other nucleic bases, as well as several amino acids, could be formed from HCN and NH3 in water, under reducing conditions.

In addition, simple sugars can be formed under putative prebiotic conditions [5], an essential feature for the emergence of nucleosides [6] and RNA (qv. the RNA world). The Butlerow reaction, i.e. the synthesis of a complex mixture of sugars (including ribose and arabinose) from formaldehyde by the action of catalysts such as calcium hydroxide, has been known since the 19th century under laboratory conditions.

#### *2.2.3. Transposing to "real" prebiotic conditions*

dioxide as reactants - originally proposed to simulate the influence of volcanic emissions - had enriched the diversity of the reaction products with seven several sulphur-containing com‐

**Figure 1.** The apparatus used by Miller and Urey in their 1953 simulated early-earth experiment on the chemical ori‐ gins of life. In the original experiment, the gases of the primitive atmosphere were: NH3, CH4, H2 and water vapor. Oth‐ er experiments were carried out under non-reducing conditions (using CO2, N2 and water) and UV exposure led to poor yields. In experiments simulating volcanic environments, Miller and Urey used H2S, CH4, NH3 and CO2 (see text).

Oró and collaborators [4] using similar experimental setups, established that adenine and other nucleic bases, as well as several amino acids, could be formed from HCN and NH3 in water,

In addition, simple sugars can be formed under putative prebiotic conditions [5], an essential feature for the emergence of nucleosides [6] and RNA (qv. the RNA world). The Butlerow reaction, i.e. the synthesis of a complex mixture of sugars (including ribose and arabinose) from formaldehyde by the action of catalysts such as calcium hydroxide, has been known since

(Graphics by Yassine Mrabet in http://en.wikipedia.org/wiki/Miller-urey\_experiment)

*2.2.2. Other "prebiotic" laboratory experiments*

the 19th century under laboratory conditions.

under reducing conditions.

pounds, including methionine and cysteine), and four amines as well.

72 Biodiversity - The Dynamic Balance of the Planet

In order to transpose from lab experiments to real life situation, several criteria must be met in order to initiate amino acid synthesis: the reactants must be concentrated enough under an aqueous environment under favorable temperature and pH conditions.

The primitive soup theory relies on a stochastic occurrence of optimal conditions for the emergence of organic life. Polymerization necessitates suitable absorbing substrates and catalysts such as metal cations and imidazole derivatives and several others, to proceed in laboratory conditions. Charged submicronic montmorillonite clay particles would have helped activated monomers to selectively concentrate (electrostatic bonds) and induce covalent polymerization. Shallow lagoons in tidal zones may theoretically provide basic chemistry. Evaporation induces concentration and promotes the formation of eutectic complexes.

Contenders of the "primitive soup" scenario advocate that life may have arisen through chemoautotrophic processes occurring in oceanic depths in the vicinity of hydrothermal settings which would provide all necessary starting conditions [7]. In this "pioneer metabo‐ lism" scenario, the generation of homochiral metalloenzymes of extant organisms from inorganic transition metal precipitates (by chelation of alpha-hydroxyl and alpha-amino acids ligands) follows a stepwise evolution by autocatalytic feedback. This "hot volcanic" prebiotic chemistry is often opposed to the "cool oceanic" chemistry that typifies the primitive soup scenario.

It appears that the composition of the primitive atmosphere is not what it was thought to be at the time of Miller's experiments, certainly not as reducing, and the conditions afforded in the hydrothermal vent environments appear more amenable to prebiotic chemistry. Oligomers could have then been formed at liquid-solid interfaces [8].

However, prebiotic chemistry under early atmospheric conditions has opened the issue towards exobiology. Scientists of repute now speculate on an extraterrestrial origin of life, or at least in the alien seeding of life essential molecular building blocks on planet earth. But this is another story.

#### *2.2.4. Before and during the RNA world*

The recent finding that ribonucleic acids (RNAs) can perform a variety of hitherto unsuspected structural and metabolic functions in cells has given credit to Walter Gilbert's prediction [9] that an all-RNA world had preceded the nucleic acid-protein world as we know it today. The fact that RNA takes evolutionary precedence on DNA (itself regarded by some as a modified RNA better suited for the conservation of genetic information), or the fact that RNAs as a catalysts (ribozymes) take precedence on enzyme catalysts, stimulate intense experimental interest.

Nucleotide monomers can theoretically be surface-assembled as oligomers [10]. The longest strands serving as templates, direct synthesis of a complementary strand starting from monomers or short oligomers, and double-stranded RNA molecules can accumulate. Disso‐ ciation of strands, one of which endowed with RNA polymerase activity, would lead to successive replication processes. Finally, the RNA world would have emerged from a mixture of activated nucleotides. However, the precise molecular mechanisms which initiated RNA oligomers in the first place, remain obscure. The monomers (nucleotides) must be activated and homochiral, before they can be assembled as strands on an absorbing mineral surface (e.g. montmorillonite clay) acting as a catalyst.

Indeed, the RNA world was probably much more chemodiverse than sometimes described (a uniform soup), notwithstanding the fact that, as said before, tidal lagoons with the presence of catalytic elements such as clay submicronic particles, or the vicinity of hydrothermal vents would greatly favor polymerization and functional gains of prebiotic organic molecules.

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Recent investigations [15] have led to the identification of many (> 100) prebiotic molecules (HCN, HCHO, glycoaldehyde etc.) in the composition of interstellar clouds and in the gasphase chemical evolution in the atmospheres of various planets (i.e. corresponding to the first step of the Miller-Urey experiment). If the radicalar processes leading to the formation of these intermediate species are simple compared to the sophisticated biochemistry involved in terrestrial chemodiversity, they remain largely unknown and should help us better understand prebiotic chemistry. Different types of molecular processes are thought to be involved, including radiative association and recombination, surface-induced processes, photon or particle induced ionization, ion-molecule reactions, photon or particle induced dissociation

Moreover, amino acids are known to occur extra-terrestrially since the 1970 discovery in the Murchison meteorite, of over 70 common and exogenous species under non-racemic propor‐ tions, some under relative abundances similar to those found with the original 1953 Miller-

This raises the problem of chirality, since on our planet, natural amino acids are all left-handed (L-amino acids). It is speculated that the prevalence of the L- form may have been influenced by polarized radiations from outer space [17]. In the laboratory, crystallization experiments in a racemic mixture always follow the same enantiomeric form as that of the initiating nucleus, further amplifying the "preference" for the L-form. Homochirality is an essential feature of

Self-organization of amphiphilic molecules (i.e. long chain fatty acids) into bilayers or into vesicles can be readily observed in laboratory conditions. In live cells, membranes provide the most elementary delineation of the self from the non self, i.e. it defines the basic identity of an individual from its environment. In non-living systems, vesicles can selectively separate solutes according to their affinities (polar or apolar) and even to their chiral properties [19].

In particular, the double layer which separates the vesicular contents from the outside can selectively extract lipophilic substances from the environment and arrange them around the inner (hydrophobic) tails. Experimentally, this feature promotes concentration of e.g. apolar

This was made possible through the activation of a multiple-component system [16].

biopolymers, for which correct folding must be required for proper function [18].

*Extra-terrestrial chemistry going organic*

and radical-molecule interactions.

**2.3. From proto-cells to living entities**

*2.3.1. Self-assembling vesicles*

*2.3.2. The amphiphilic double layer*

Urey experiment.

Interestingly, other nucleotide-like structures that may be formed under prebiotic conditions can reasonably qualify as RNA functional analogues and have been termed "alternative genetic systems" [11].

The existence in prebiotic conditions of AMP-derived cofactors that have acquired amino acidlike properties through post-translational modifications is possible, since these cofactors participate at all levels in the metabolism of extant life forms. As Maurel and Haenni [12] put it," Coenzymes would be vestiges of catalytic nucleic enzymes that preceded ribosomal protein synthesis, and tRNAs can be viewed as large coenzymes participating in the transfer of amino acids."

Ligand-substrate recognition must have followed from the selection of *aptamers* (molecules that bind specifically to one target molecule) from a pool of oligonucleic acids or peptides. Artificial selection of adenine-dependent ribozyme aptamers [13 ] indicates that the use of small exogenous cofactors (adenine) by ribozymes could have actively contributed to the expansion of the catalytic and metabolic repertoires of RNA species in the prebiotic RNA world. Modern catalytic equivalents of ribozymes are metalloenzymes, and adenine fills the same cofactor function as histidine.

**Figure 2.** A depiction of the step-by step scenario involved in the origin of life on earth, attempting to integrate the "metabolist" scenario into the "primitive soup" scheme (from: Bada and Lazcano, [14])

Indeed, the RNA world was probably much more chemodiverse than sometimes described (a uniform soup), notwithstanding the fact that, as said before, tidal lagoons with the presence of catalytic elements such as clay submicronic particles, or the vicinity of hydrothermal vents would greatly favor polymerization and functional gains of prebiotic organic molecules.

#### *Extra-terrestrial chemistry going organic*

ciation of strands, one of which endowed with RNA polymerase activity, would lead to successive replication processes. Finally, the RNA world would have emerged from a mixture of activated nucleotides. However, the precise molecular mechanisms which initiated RNA oligomers in the first place, remain obscure. The monomers (nucleotides) must be activated and homochiral, before they can be assembled as strands on an absorbing mineral surface (e.g.

Interestingly, other nucleotide-like structures that may be formed under prebiotic conditions can reasonably qualify as RNA functional analogues and have been termed "alternative genetic

The existence in prebiotic conditions of AMP-derived cofactors that have acquired amino acidlike properties through post-translational modifications is possible, since these cofactors participate at all levels in the metabolism of extant life forms. As Maurel and Haenni [12] put it," Coenzymes would be vestiges of catalytic nucleic enzymes that preceded ribosomal protein synthesis, and tRNAs can be viewed as large coenzymes participating in the transfer of amino

Ligand-substrate recognition must have followed from the selection of *aptamers* (molecules that bind specifically to one target molecule) from a pool of oligonucleic acids or peptides. Artificial selection of adenine-dependent ribozyme aptamers [13 ] indicates that the use of small exogenous cofactors (adenine) by ribozymes could have actively contributed to the expansion of the catalytic and metabolic repertoires of RNA species in the prebiotic RNA world. Modern catalytic equivalents of ribozymes are metalloenzymes, and adenine fills the

**Figure 2.** A depiction of the step-by step scenario involved in the origin of life on earth, attempting to integrate the

"metabolist" scenario into the "primitive soup" scheme (from: Bada and Lazcano, [14])

montmorillonite clay) acting as a catalyst.

74 Biodiversity - The Dynamic Balance of the Planet

same cofactor function as histidine.

systems" [11].

acids."

Recent investigations [15] have led to the identification of many (> 100) prebiotic molecules (HCN, HCHO, glycoaldehyde etc.) in the composition of interstellar clouds and in the gasphase chemical evolution in the atmospheres of various planets (i.e. corresponding to the first step of the Miller-Urey experiment). If the radicalar processes leading to the formation of these intermediate species are simple compared to the sophisticated biochemistry involved in terrestrial chemodiversity, they remain largely unknown and should help us better understand prebiotic chemistry. Different types of molecular processes are thought to be involved, including radiative association and recombination, surface-induced processes, photon or particle induced ionization, ion-molecule reactions, photon or particle induced dissociation and radical-molecule interactions.

Moreover, amino acids are known to occur extra-terrestrially since the 1970 discovery in the Murchison meteorite, of over 70 common and exogenous species under non-racemic propor‐ tions, some under relative abundances similar to those found with the original 1953 Miller-Urey experiment.

This was made possible through the activation of a multiple-component system [16].

This raises the problem of chirality, since on our planet, natural amino acids are all left-handed (L-amino acids). It is speculated that the prevalence of the L- form may have been influenced by polarized radiations from outer space [17]. In the laboratory, crystallization experiments in a racemic mixture always follow the same enantiomeric form as that of the initiating nucleus, further amplifying the "preference" for the L-form. Homochirality is an essential feature of biopolymers, for which correct folding must be required for proper function [18].

#### **2.3. From proto-cells to living entities**

#### *2.3.1. Self-assembling vesicles*

Self-organization of amphiphilic molecules (i.e. long chain fatty acids) into bilayers or into vesicles can be readily observed in laboratory conditions. In live cells, membranes provide the most elementary delineation of the self from the non self, i.e. it defines the basic identity of an individual from its environment. In non-living systems, vesicles can selectively separate solutes according to their affinities (polar or apolar) and even to their chiral properties [19].

#### *2.3.2. The amphiphilic double layer*

In particular, the double layer which separates the vesicular contents from the outside can selectively extract lipophilic substances from the environment and arrange them around the inner (hydrophobic) tails. Experimentally, this feature promotes concentration of e.g. apolar amino acids and their non-enzymatic condensation into dipeptides or small oligopeptides within the lipid bilayer. In addition, vectorial properties in phospholipidic vesicles are thought to influence the inner pH (making it lower than outer pH) in small vesicles, due to differences in the behavior of water molecules.

Chemodiversity as we know it today is mostly organic and is the result of complex biochemical processes within living organisms that must constantly adapt to changing environments and

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Our chemodiversity is usually classified as mineral or organic. Exploitable minerals are solidified in the earth crust or deposited as sediments or conglomerates - geochemical cycles connect the molten inner core of the planet with the biosphere through the displacement of continental plates and volcanic activity. Organic chemodiversity is concentrated in the biosphere, as the result of the present and past metabolic processes of marine and terrestrial organisms. Chemically, organic molecules are carbon atoms and scaffolds of connected carbon atoms, linked to hydrogen and covalently to heteroatoms e.g. oxygen, nitrogen, atoms but also to sulfur, phosphorus and halogens or metal complexes (*coordination chemistry*) to form functional groups. Larger organic molecules often adopt three-dimensional architectures that confer them with the exquisite specificity required for recognition and binding to a defined molecular target. Organic natural products are by far the largest contributors to marine and terrestrial chemodiversity, and also the most labile in the face of anthropic and natural

The chemistry of our oceans has evolved considerably [22], especially with the gradual production of oxygen, which initially oxidized mantle rocks and dissolved reduced metals such as iron then tended to precipitate, as evidenced by red strata in ancient sediment beds. Free oxygen then started to rise in atmospheric concentrations, some of which was split by cosmic radiations to form the protective ozone layer. Respiration became possible and some life forms moved out of the oceans, and both aquatic and terrestrial species diversification started, and with it, organic chemodiversity. It should be emphasized that combustion occurs at oxygen levels only above 15% and organic matter would spontaneously burn at 25% concentrations - which explains that life is possible only if the present level (21%) is maintained around 20% and if genotoxic radiations can be efficiently filtered out. Oxygen is also toxic at the cellular level, if the production of (or exposure to) reactive oxygen species (ROS) or oxygen radicals cannot be counterbalanced by antioxidants or if the resulting damages cannot be repaired. When involved in regular intracellular signaling, ROS can be involved in the activation of defense metabolic pathways, and contribute to the enrichment of the metabolic

With the exception of very few extremophiles that can live under elevated temperatures (above 80°C) and hyper acidic environments pH < 2), most microorganisms are not tolerant to

**3. Chemodiversity explodes with the emergence of life**

influences that affect the stability of our ecosystems.

repertoire of planktonic and benthic organisms.

**3.3. Biochemistry operates under very specific conditions**

**3.2. "Cool" oxygen biochemistry**

compete for their survival.

**3.1. "Cool" carbon chemistry**

**Figure 3.** A phospholipid vesicle, with a double-layered membrane. Each layer includes a hydrophilic head (dark knobs) and a hydrophobic tail made up of long lipid chains. The aqueous environment inside the vesicle isolates en‐ trapped metabolites, biopolymers and catalysts, the whole structure acting as a reaction vessel.

#### *2.3.3. Vesicles as proto-cells*

The total synthesis of a simple cell is possibly the ultimate challenge in synthetic biology. It is experimentally possible to entrap nucleic acids inside self - forming phospholipid vesicles, acting as reaction vessels for e.g. polymerase chain reaction, enzymatic RNA replication and even protein synthesis, as demonstrated by Oberholzer and collaborators (reviewed in [19]). The molecular pump scenario [20], in which peptides were initially synthesized through a molecular engine could also have taken place inside such structures. In nature, the inclusion of clay microparticles acting as catalysts is highly probable. Thus, phospholipid vesicles can be regarded as useful experimental models of proto-cells [21], but many questions still need addressing before considering them as early precursors of living cells.

*Protobiology* uses a bottom up approach when designing complex and functional protocells from simple molecules and organic catalysts.

*Synthetic biology* uses a top-down approach to identify the minimal components of living cells that will qualify, in other words to rediscover the basic cell before it underwent the complexities of Darwinian evolution. Thus protocells are of exciting biotechnological interest in the quest to optimize chemotherapies (cellular target recognition, kinetics of drug delivery).

Prebiotic chemistry is certainly more complex than previously thought, and chemodiversity has undergone periods of expansion, especially through stochastic combinations during the so-called RNA world, and during the development of proto-cells.

Chemodiversity as we know it today is mostly organic and is the result of complex biochemical processes within living organisms that must constantly adapt to changing environments and compete for their survival.
