Deep-sea secrets of butane metabolism

Anaerobic microbes have been found to break down the hydrocarbon butane by a pathway with some similarities to anaerobic methane breakdown. Harnessing the butane pathway might enable biofuel generation. See Article p.396

Microbes living in anaerobic conditions, such as in deep-sea sediments, need a way of generating energy that does not require oxygen gas. Some anaerobic microbes do this by breaking down methane to form carbon dioxide1. Others2 obtain energy by metabolizing the hydrocarbon butane (C4H10), but the butane-breakdown pathway has until now been unknown. Determining how butane is metabolized might be useful for making biofuels or for developing efficient catalysts for hydrocarbon activation (the process of breaking a hydrocarbon's chemical bonds). On page 396, Laso-Pérez et al.3 report the pathway for microbial anaerobic breakdown of butane to CO2. The authors identify some butane-breakdown steps ripe for further investigation, and observe that some similar steps have evolved in the microbial processes for degrading methane and butane.

Laso-Pérez and colleagues obtained deep-sea sediment samples from the Gulf of California and isolated fractions that could degrade butane. The butane degradation they observed depended on a microbial consortium formed of Candidatus Syntrophoarchaeum archaea and HotSeep-1 bacteria, two types of prokaryote (organisms lacking a nucleus). The authors found that the microbial consortium can also metabolize propane (C3H8), although it is not known whether propane and butane are degraded by the same enzymes or by different enzymes that have specific substrate preferences. However, the consortium does not degrade methane, nor several other short-chain hydrocarbons the authors tested.

Butane consists of carbon and hydrogen atoms linked by strong single bonds, and the molecule lacks a reactive group. The stability of the carbon–hydrogen (C–H) bond poses a formidable and interesting chemical challenge in butane breakdown. For anaerobic microbial breakdown of methane, the thermodynamically unfavourable hydrocarbon breakdown proceeds by coupling it to a thermodynamically favourable reaction: for example, the transfer of electrons to sulfate to form hydrogen sulfide (H2S, a reduced form of sulfate)4,5. Laso-Pérez and colleagues investigated whether such thermodynamic coupling might occur in their microbial consortium, and found evidence for sulfate reduction that depended on butane breakdown. In anaerobic methane degradation, sulfate reduction occurs by direct interspecies electron transfer3,4 from the archaea to their bacterial partner HotSeep-1. Laso-Pérez and colleagues find no evidence for sulfate-reduction genes in the archaea they studied, and propose that an interspecies electron-transfer mechanism also occurs in the butane-degradation pathway.

The authors determined experimentally that the overall butane-breakdown reaction consists of the conversion of butane, sulfate and hydrogen ions to final products of CO2, H2S and water. On the basis of clever identification of genes that might have a role in the butane-degradation pathway and determination of possible intermediate compounds and cofactors, Laso-Pérez et al. propose a complete degradation pathway from butane to CO2 in Candidatus Syntrophoarchaeum. The authors identify some key stages in the degradation of pathway intermediates (Fig. 1).

Figure 1: Proposed pathway for butane breakdown.

Laso-Pérez et al.3 propose a pathway for the anaerobic breakdown of butane in a microbial consortium formed between Candidatus Syntrophoarchaeum archaeal microbes and HotSeep-1 bacteria. Although the overall reaction in Candidatus Syntrophoarchaeum is thermodynamically unfavourable, the reaction proceeds by coupling to a thermodynamically favourable reaction in HotSeep-1 bacteria. The initial butane cleavage, a step known as hydrocarbon activation, creates a butane derivative bound to coenzyme M (butyl–CoM). The authors propose that butane activation is catalysed by an enzyme similar to methyl coenzyme M reductase (MCR). Through unknown steps, the intermediate butyl–CoM is converted to butyryl–CoA, which then undergoes four steps of fatty-acid oxidation to form acetyl–CoA. Wood–Ljungdahl pathway7 enzymes convert acetyl–CoA to carbon dioxide and a methyl group bound to the coenzyme tetrahydromethanopterin (H4MPT). This methyltetrahydromethanopterin derivative is then converted by Wolfe-cycle8 enzymes to CO2 in a process related to the methane degradation pathway known as reverse methanogenesis1. In the microbial butane-degradation pathway, the Wood–Ljungdahl pathway enzymes and Wolfe-cycle enzymes act to degrade, rather than synthesize, their normal products. These enzyme reversals occur when these reactions are coupled to the thermodynamically favourable reduction of sulfate to hydrogen sulfide, which occurs through interspecies electron transfer to HotSeep-1 bacteria.

The first step in butane degradation involves the breakage of one of butane's C–H single bonds. In methane degradation, C–H bond activation is catalysed by the enzyme methyl coenzyme M reductase (MCR), resulting in the formation of a methyl group bound to coenzyme M (CoM)6. Laso-Pérez et al. tested whether CoM might also be associated with butane breakdown. Using mass spectrometry, they identified a butane derivative bound to CoM (butyl–CoM) in their microbial sample. The authors also observed that a CoM-mimic molecule, bromoethanesulfonate, inhibits butane degradation. These results strongly implicate the catalytic action of an enzyme similar to MCR in the initial C–H bond cleavage of butane.

The next stage of the breakdown process, the multi-step conversion of butyl–CoM to a derivative bound to coenzyme A (CoA), known as butyryl–CoA, constitutes the most notable mechanistic uncertainty in the pathway described by Laso-Pérez and colleagues. During this sequence, a butane-derived group is transferred from CoM to the ubiquitous CoA. One option is that a butyltransferase enzyme known as Mta catalyses this reaction by transferring the butyl group to CoA, which generates butyl–CoA. However, it seems more probable that butyl–CoM undergoes oxidation to generate butyryl–CoM, and that the CoM is subsequently displaced by CoA to generate butyryl–CoA.

The authors propose that fatty-acid oxidation steps convert butyryl–CoA to the common metabolic intermediate acetyl–CoA. Then Wood–Ljungdahl pathway7 enzymes oxidize acetyl–CoA, resulting in the formation of CO2 and a methyl group bound to the coenzyme tetrahydromethanopterin (H4MPT). The final steps of the pathway involve the action of Wolfe-cycle enzymes8, which oxidize the methyltetrahydromethanopterin, resulting in the formation of CO2.

An enzyme is usually thought of as catalysing a directional reaction that transforms molecule A into molecule B. However, an enzyme actually catalyses a reaction in a state of equilibrium, and if the equilibrium changes, the enzyme can run in reverse and transform molecule B into molecule A. Two of the key metabolic modules in the proposed butane-degradation pathway involve reactions that are best known for running in the opposite direction. In the butane-degradation process, Wood–Lungdahl enzymes degrade acetyl–CoA, although they usually synthesize acetyl–CoA. Similarly, during butane degradation, Wolfe-cycle enzymes uncharacteristically degrade rather than synthesize a methyl group. This reverse action of Wolfe-cycle enzymes is also observed during methane degradation by anaerobic microbes in the process known as reverse methanogenesis1.

A particularly interesting enzyme-reversal question arising from this research is whether any 'butanogenic' microbes might naturally exist, or could be engineered, that could run the entire butane-degradation pathway in reverse, thereby generating butane biofuel. A butane-synthesizing reaction would be thermodynamically favourable, and would not require coupling to sulfate reduction.

Laso-Pérez and colleagues' analysis of the anaerobic consortium that degrades butane provides a glimpse into a pathway for the oxygen-independent breakdown of short-chain hydrocarbons. The authors provide evidence that butane oxidation is linked to sulfate reduction. It will be interesting to investigate whether butane oxidation is coupled to other types of reduction process, such as the reduction of nitrate or metal that occurs in reverse methanogenesis9. Further biochemical studies of butane metabolism might lead to major advances in the design of efficient catalysts for hydrocarbon activation, or enable the use of CO2 to generate butane or other intermediate compounds in this pathway.Footnote 1


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Correspondence to Stephen W. Ragsdale.

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Ragsdale, S. Deep-sea secrets of butane metabolism. Nature 539, 367–368 (2016). https://doi.org/10.1038/539367a

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