The rocky roots of the acetyl-CoA pathway

TLDR: It is suggested that primordial biochemistry was housed in an acetate-producing hydrothermal reactor that retained reduced carbon compounds produced within its naturally forming inorganic confines.

About: This article is published in Trends in Biochemical Sciences.The article was published on 2004-07-01 and is currently open access. It has received 362 citations till now. The article focuses on the topics: Carbon monoxide dehydrogenase.

Figures

Figure 2. Structural similarity between (Fe,Ni)S centres in enzymes and in minerals. (a) Cartoon of the carbon monoxide dehydrogenase (CODH) and acetyl-coenzyme-A (CoA) synthetase (ACS) reaction, based on structural data summarized in Refs [16–20,35]. The exact reaction mechanism for ACS has not been resolved: differing proposals have been put forth [17,20] and differences have been also reported regarding the presence of copper, zinc and nickel at the active site of the A cluster [17,20,35]; nickel has been found at the active site of the active enzyme [18]. Only selected metal sulphide centres of CODH and ACS are shown; the protein structure is represented by shading. The structures of methylsulphide, which has been synthesized from H2S and CO2 via FeS catalysis [24], and methyl thioacetate (acetyl methylsulphide), which has been synthesized from CO and methylsulphide via NiS and FeS catalysis [25], are shown at the top for comparison. A reaction mechanism for the latter mineral-catalysed synthesis has been proposed [25]. (b) Structure of the Fe4 2.5þS4 ‘cubane’ unit in a half cell of the metastable mineral greigite (SNiS)(Fe4S4)(SFeS); see Ref. [10] for further structural details and comparisons. (c) The Fe4S4 ‘thiocubane’ units in other proteins that catalyse reactions of relevance to the acetyl-CoA pathway, namely, a ferredoxin [21], an [FeNi]-hydrogenase [22], and an iron-only [Fe]-hydrogenase [23], the proposed active site of which is called the ‘H-cluster’.

Figure 1. Naturally formed iron sulphide compartments. (a) Top view of a fossilized, 350-Myr-old iron–sulphur deposit from Tynagh, Ireland, that formed at a hydrothermal spring on the seafloor [10]. It comprises botryoids (the bubble-laden surface) and chimneys (arrows), through which the hydrothermal waters exhaled, leading to the iron sulphide deposit. Although ten times younger than the first life on Earth, this mineral sample illustrates the dynamics of deposition at seafloor hydrothermal mounds. The inset in Figure 3 might have looked similar, if viewed from the top. (b,c) Electron micrographs of a section of a Tynagh botryoid [10], showing the naturally formed, metal-sulphide-bounded compartments. Scale bar in (a) ¼ 1 cm; scale bar in (c) ¼ 100 mm.

Figure 3. The kind of natural hydrothermal reactor developed at an alkaline submarine spring, proposed here to be the geological hatchery of life. Gradients in temperature (110 to 20 8C), pH (10 to 6) and redox (2600 mV to þ100 mV) are steepest at the mound’s exterior. The mound comprises carbonates, clays, iron oxyhydroxides and sulphides. Ionized and polar organic molecules are synthesized, concentrated, and ordered in the reactor [10,11]. Waste heat, water, unionized and nonpolar organic products, and much of the acetate are exhaled through self-forming chimneys. Inset shows an enlargement of one of the vents.

Frequently asked questions

Q1. What are the contributions mentioned in the paper "The rocky roots of the acetyl-coa pathway" ?

Here the authors propose that biochemistry got started when the two volatiles that were thermodynamically furthest from equilibrium on the early Earth – namely, marine CO2 from volcanoes and hydrothermal H2 – met at a hydrothermal vent rich in metal sulphides. The authors suggest that primordial biochemistry was housed in an acetate-producing hydrothermal reactor that retained reduced carbon compounds produced within its naturally forming inorganic confines. 

Q2. What have the authors stated for future works in "The rocky roots of the acetyl-coa pathway" ?

For anything like a cell ever to emerge, the building blocks of biochemistry would have to have a continuous source of reduced carbon and energy and would have to remain concentrated at their site of sustained synthesis over extended times. Given the structural ( and catalytic ) similarity betweenthemineralsthemselvesandthecatalyticcentresof the enzymes in the acetyl-CoA pathway, an attractive idea is that the first cells simply conserved a thermodynamically favourable reaction that got started in a stable geochemical reactor with catalytic walls and a strong, sustained redox potential: in other words, in an acetate-producing hydrothermal mound. 

Q3. What is the likely explanation for the hydrothermal reactor?

But chemical energy from acetate production could nonetheless have been harnessed, provided that organic thiols were available in the reactor, which is extremely likely, for example, in the form of methylsulphide [24]. 

Q4. What would be the way to get started with biochemistry?

For anything like a cell ever to emerge, the building blocks of biochemistry would have to have a continuous source of reduced carbon and energy and would have to remain concentrated at their site of sustained synthesis over extended times. 

Q5. What is the role of the acetyl-CoA pathway?

Given that FeS and NiS can catalyse synthesis of methanethiol from CO2 and H2S [24] and the synthesis of the thioester acetyl methylsulphide from CO and CH3SH in the laboratory [25], all of the constituents for a primordial role of the acetyl-CoA pathway seem to be in place. 

Q6. What is the way to start about the business of progressing from inorganic chemistry?

If the authors assume that ammonia was available in the hydrothermal fluid as the product of N2 reduction at high temperature and pressure deep in the crust [13], plus a bitof phosphate derived from the ocean, then with a large and continuous flux through this exergonic pathway, enough organic ‘leftovers’ could accumulate to start about the business of progressing from inorganic chemistry to the chemistry of life. 

Q7. What is the simplest explanation for the pathway?

In a nutshell, the pathway reduces CO2 to form an energy-rich thioester in the presence of a thiol with the help of electrons supplied by H2, while releasing enough energy to make ATP via chemiosmosis in the process. 

Q8. How can acetate be produced from CO and CH3SH?

Both the thioester acetyl methylsulphide (CH3COSCH3) and its hydrolysed product, acetate (CH3COO2), can be produced from CO and CH3SH by using only FeS and NiS as catalysts [25]. 

Q9. What is the common view of the first biochemical pathway?

Traditional views point to glycolytic-like fermentations as the source of carbon and energy [3], and pyrite formation coupled to a reverse citric acid cycle (a pathway of CO2 fixation in some prokaryotes), which has construable similarities to imaginable inorganic reactions, has also been proposed [4,14]. 

Q10. What is the significance of the compartments in the hydrothermal reactor model?

The significance of the 3D compartments comprising the reactor (Figures 1 and 3), which form a barrier to diffusion into the ocean, is their retention of just-synthesized organic molecules. 

Q11. What is the origin of the acetyl-coa pathway?

In this ‘hydrothermal reactor’ hypothesis, a primitive, inorganically catalysed analogue of the exergonic acetyl-CoA pathway, using H2 as the initial electron donor and CO2 as the initial acceptor, was instrumental in the synthesis of organic precursors to fuel primordial biochemical reactions. 

Q12. What is the attractive idea for the acetyl-CoA pathway?

The acetyl-CoA pathway as an initial biochemical route is also attractive because it does not require pre-existing organic ‘primers’, such as intermediates of the citric acid cycle, to operate. 

Q13. What is the role of pyrophosphates in biochemistry?

The thermodynamically favourable production of thioesters as highly reactive, energy-rich intermediates would fit very well with De Duve’s [7] suggestions that thioesters were central to early biochemistry, but would exclude neither a role for pyrophosphates as early energy stores [34] nor a role for additional redox potential stemming from photolytically generated marine Fe(III) [21]. 

Q14. What is the problem with the transition from disorganized solutions of organic molecules to free-living cells?

Another related problem is the transition from disorganized solutions of organic molecules to free-living cells, which are always surrounded by a biological membrane and are always dependent on reduction– oxidation (redox) reactions involving an electron donor and electron acceptor.