TotM: mtaA from Methanosarcina acetivorans, ancient metabolism and a dreadful prophecy

cthulhu.pngRejoice everyone, for the stars are soon to be aligned and Great Cthulhu shalt awake from its eternal dream. Enjoy thy sanity while thou can, before the Great Old One raises from the eternal city R’lyeh and scratches the thin veil of the cognoscible! Iä! Iä! Cthulhu fhtagn! Ph'nglui mglw'nfah Cthulhu R'lyeh wgah'nagl fhtagn! Cthulhu is the most famous creature that lurked the imagination of the american horror writer Howard Phillips Lovecraft, considered the father of the cosmic horror genre. Cthulhu is an alien entity quite often compared to a god that is, literally, beyond human comprehension. It’s one of the Great Old Ones, a title shared by other horrific entities with strambotic names such as Yog-Sothoth, Azathoth, Shub-Niggurath, Hastur or Nyarlathotep; and whose motivations are incomprehensible for the human mind. The focus on describing the impossibility of understanding such beings is not trivial. Cthulhu and company are so alien that they are not bound by concepts so basics as euclidian geometry, and thus any fool that may attempt to grasp their true nature will invariably corrupt his or her own sanity. The main theme in Lovecraft’s work is the horror of realizing the insignificance of humanity itself, vulnerables as we are drifting in an endless cosmic foam in our tiny planetary bubble.


Cthulhu_sketch_by_Lovecraft.jpgThe notion of an ancient creature awakening from a long dream and bringing the end of the world as we know it is a common trope in cosmic horror stories, but it is actually a very accurate metaphor of our future as species. Industry, agriculture, deforestation and many other human activities are slowly changing the composition of our atmosphere and the climate of the whole planet. Most of these emissions come in the form of carbon dioxide, a gas that has the property of reflecting infrared electromagnetic waves that would otherwise be sent back to space, causing the planet to heat up slowly. Scientist have tried to convince governments to take drastic measures in order to prevent such nefarious prophecy. Unfortunately, the response has ranged from insufficient to something akin to the tramped babbling of Daemon Sultan Azathoth. However, while carbon dioxide emissions are a great problem in themselves, they are just the key that will bring something much worse to our world. Methanogenic archaea (from greek ἀρχαῖος, meaning ancient) are a diverse group of anaerobic microorganisms that have the ability to produce methane as a byproduct of their metabolism. Methane is a much more powerful greenhouse gas that carbon dioxide and there is plenty of it hidden in arctic soils, encased for millennia in an ice seal. With the temperature of the planet increasing by carbon emissions, the frozen tomb of all that methane will eventually thaw. And while there is great academic debate about the exact consequences of such event, just like Cthulhu and company we know that it will not be pretty for our species.


frozen_methaneTurning back to methanogenesis, the pathway itself is expected to be very ancient, having originated at a time before cyanobacterial activity filled the atmosphere of our planet with poisonous oxygen. Until very recently it was considered to be exclusive of organisms in the domain Archaea, although some recent lines of evidence point to a wider distribution of the enzymes and suggest it may have been part of the metabolic pool of the last universal common ancestor (LUCA) (Lever, 2016). The pathway is really alien too, compared with what we are used to deal in biology. It uses as electron donors a wide array of simple compounds that usually are the fermentation byproducts of other microbes, such as molecular hydrogen, methylated small organic molecules, formate or acetate. Methanogens are able to use such compounds as both carbon sources and energy sources, reducing carbon dioxide to methane in the process. The net energetic balance of the pathway is extremely low. If we assume that LUCA was a methanogen, the low energetic yield of the pathway may explain why it has been lost so many times during evolution. Acetate dependent (acetoclastic) methanogenesis is the most common form of methanogenesis, and is restricted to members of the genera Methanosarcina and Methanosaeta. These organisms perform the very last step in the process of organic matter decay in anaerobic conditions. Beyond their biogeochemical relevance, they are often used in important industrial processes, such as water treatment or biogas production.


methanosarcinaEven more interesting is how bizarre and alien are the enzymes in the pathway. Despite the apparent simplicity of the chemical reaction, the pathway involves many enzymes with extremely unusual properties, including weird amino acids (pyrrolysine), very unusual cofactors, many subunits. Many of the enzymes in the pathway are also very different to any other protein family, making very difficult to understand the origin and evolution of such an enigmatic pathway. Regarding the utilized substrate, all methanogenic pathways converge with the transference of a methyl group to a carrier molecule called coenzyme M. The metabolic reactions from methyl coM to methane are shared by all methanogenic pathways. The protein mtaA (Methylcobamide:CoM methyltransferase isozyme M) from Methanosarcina acetivorans is a membrane enzyme that catalyzes the last unique step of the acetoclastic methanogenesis. This reaction is the exergonic and reversible transference of a methyl group from 5-methyl-tetrahydrosarcinapterin to the coenzyme M. The reaction is coupled to a sodium pump, generating a sodium membrane gradient that is used to produce energy through an ATP synthase. The protein contains an uroporphyrinogen cofactor and, as we can observe in our tree of the month from the Quest for Orthologs Methanosarcina acetivorans phylome. It shares distant homology with porphyrin biosynthesis enzymes in eukaryotes. Fortunately for us, despite how alien and powerful methanogenesis is for our planet, its study is no riskier for our sanity that any other microbial activity. Ïa, Ïa, Methanosarcina fhatgn!




Cthulhu and R'lyeh, by Bendukiwi. CC 3.0 license.

Sketch of Cthulhu, by H. P. Lovecraft. Public domain.

Frozen methane bubbles. Public domain.

Scan electron micrography of Methanosarcina barkeri. Public domain.