Syntrophy

{{short description|Cooperation between microbial species to digest a substrate}}

In [[biology]], '''syntrophy''',<ref name=":0">{{Citation |last1=Gentry |first1=Terry J. |title=Chapter 19 - Microbial Diversity and Interactions in Natural Ecosystems |date=2015-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780123946263000193 |work=Environmental Microbiology (Third Edition) |pages=441–460 |editor-last=Pepper |editor-first=Ian L. |access-date=2023-12-27 |place=San Diego |publisher=Academic Press |doi=10.1016/b978-0-12-394626-3.00019-3 |isbn=978-0-12-394626-3 |last2=Pepper |first2=Ian L. |last3=Pierson |first3=Leland S. |editor2-last=Gerba |editor2-first=Charles P. |editor3-last=Gentry |editor3-first=Terry J.|url-access=subscription }}</ref><ref name=":1">{{Citation |last=Marietou |first=Angeliki |title=Chapter Two - Sulfate reducing microorganisms in high temperature oil reservoirs |date=2021-01-01 |url=https://www.sciencedirect.com/science/article/pii/S006521642100006X |journal=Advances in Applied Microbiology |volume=116 |pages=99–131 |editor-last=Gadd |editor-first=Geoffrey Michael |access-date=2023-12-27 |publisher=Academic Press |doi=10.1016/bs.aambs.2021.03.004 |pmid=34353505 |editor2-last=Sariaslani |editor2-first=Sima|url-access=subscription }}</ref><ref name="Schink_2013" /><ref name="Kamagata_2015" /> '''syntrophism''',<ref name=":0" /><ref name=":2">{{Cite web |date=2022-09-30 |title=syntrophism {{!}} biology {{!}} Britannica |url=https://www.britannica.com/science/syntrophism |access-date=2023-12-27 |archive-url=https://web.archive.org/web/20220930004228/https://www.britannica.com/science/syntrophism |archive-date=2022-09-30 }}</ref><ref>{{Cite web |date=2022-08-19 |title=Syntrophism Definition & Meaning {{!}} Merriam-Webster Medical |url=https://www.merriam-webster.com/medical/syntrophism |access-date=2023-12-27 |archive-url=https://web.archive.org/web/20220819204804/https://www.merriam-webster.com/medical/syntrophism |archive-date=2022-08-19 }}</ref> or '''cross-feeding'''<ref name=":0" /> ({{ety|el|syn|together||trophe|nourishment}}) is the cooperative interaction between at least two [[microbial]] species to degrade a single [[Substrate (biology)|substrate]].<ref name=":1" /><ref name="Schink_2013" /><ref name="Kamagata_2015">{{cite book | vauthors = Kamagata Y | chapter = Syntrophy in Anaerobic Digestion |date=2015-03-15 |chapter-url=https://www.worldscientific.com/doi/abs/10.1142/9781783267910_0002 | title = Anaerobic Biotechnology |pages=13–30 |publisher=Imperial College Press |doi=10.1142/9781783267910_0002 |isbn=978-1-78326-790-3 |access-date=2022-11-11}}</ref><ref>{{cite journal | vauthors = Hao L, Michaelsen TY, Singleton CM, Dottorini G, Kirkegaard RH, Albertsen M, Nielsen PH, Dueholm MS | display-authors = 6 | title = Novel syntrophic bacteria in full-scale anaerobic digesters revealed by genome-centric metatranscriptomics | journal = The ISME Journal | volume = 14 | issue = 4 | pages = 906–918 | date = April 2020 | pmid = 31896784 | pmc = 7082340 | doi = 10.1038/s41396-019-0571-0 | bibcode = 2020ISMEJ..14..906H }}</ref> This type of [[biological interaction]] typically involves the transfer of one or more [[metabolic intermediate]]s between two or more metabolically diverse microbial species living in close proximity to each other.<ref name="Schink_2013">{{cite book | vauthors = Schink B, Stams AJ | chapter = Syntrophism Among Prokaryotes |date=2013 | title = The Prokaryotes: Prokaryotic Communities and Ecophysiology |pages=471–493 | veditors = Rosenberg E, DeLong EF, Lory S, Stackebrandt E |place=Berlin, Heidelberg |publisher=Springer |language=en |doi=10.1007/978-3-642-30123-0_59 |isbn=978-3-642-30123-0 | chapter-url = http://nbn-resolving.de/urn:nbn:de:bsz:352-276499 }}</ref><ref name=":2" /> Thus, syntrophy can be considered an obligatory interdependency and a mutualistic metabolism between different microbial species, wherein the growth of one partner depends on the [[nutrient]]s, [[growth factor]]s, or substrates provided by the other(s).<ref>{{cite journal | vauthors = Dolfing J | title = Syntrophy in microbial fuel cells | journal = The ISME Journal | volume = 8 | issue = 1 | pages = 4–5 | date = January 2014 | pmid = 24173460 | pmc = 3869025 | doi = 10.1038/ismej.2013.198 | bibcode = 2014ISMEJ...8....4D }}</ref><ref name="Morris_2013">{{cite journal | vauthors = Morris BE, Henneberger R, Huber H, Moissl-Eichinger C | title = Microbial syntrophy: interaction for the common good | journal = FEMS Microbiology Reviews | volume = 37 | issue = 3 | pages = 384–406 | date = May 2013 | pmid = 23480449 | doi = 10.1111/1574-6976.12019 | doi-access = free }}</ref>

== Microbial syntrophy == Syntrophy is often used synonymously for mutualistic [[symbiosis]] especially between at least two different bacterial species. Syntrophy differs from [[symbiosis]] in a way that syntrophic relationship is primarily based on closely linked metabolic interactions to maintain thermodynamically favorable lifestyle in a given environment.<ref>{{cite journal | vauthors = Sieber JR, McInerney MJ, Gunsalus RP | title = Genomic insights into syntrophy: the paradigm for anaerobic metabolic cooperation | journal = Annual Review of Microbiology | volume = 66 | pages = 429–452 | date = 2012 | pmid = 22803797 | doi = 10.1146/annurev-micro-090110-102844 }}</ref><ref name="McInerney_2009">{{cite journal | vauthors = McInerney MJ, Sieber JR, Gunsalus RP | title = Syntrophy in anaerobic global carbon cycles | journal = Current Opinion in Biotechnology | volume = 20 | issue = 6 | pages = 623–632 | date = December 2009 | pmid = 19897353 | pmc = 2790021 | doi = 10.1016/j.copbio.2009.10.001 }}</ref><ref>{{cite journal | vauthors = McInerney MJ, Rohlin L, Mouttaki H, Kim U, Krupp RS, Rios-Hernandez L, Sieber J, Struchtemeyer CG, Bhattacharyya A, Campbell JW, Gunsalus RP | display-authors = 6 | title = The genome of Syntrophus aciditrophicus: life at the thermodynamic limit of microbial growth | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 18 | pages = 7600–7605 | date = May 2007 | pmid = 17442750 | pmc = 1863511 | doi = 10.1073/pnas.0610456104 | doi-access = free | bibcode = 2007PNAS..104.7600M }}</ref> Syntrophy plays an important role in a large number of microbial processes especially in oxygen limited environments, methanogenic environments and anaerobic systems.<ref name="McInerney_2019">{{cite journal | vauthors = McInerney MJ, Sieber JR, Gunsalus RP | title = Syntrophy in anaerobic global carbon cycles | journal = Current Opinion in Biotechnology | volume = 20 | issue = 6 | pages = 623–632 | date = December 2009 | pmid = 19897353 | pmc = 2790021 | doi = 10.1016/j.copbio.2009.10.001 | series = Chemical biotechnology ● Pharmaceutical biotechnology }}</ref><ref name="Worm_2010">{{Cite book | vauthors = Worm P, Müller N, Plugge CM, Stams AJ, Schink B | chapter = Syntrophy in methanogenic degradation. | title = (Endo)symbiotic Methanogenic Archaea | date = 2010 | pages = 143–173 | publisher = Springer | location = Berlin, Heidelberg |series=Microbiology Monographs |volume=19 |language=en |doi=10.1007/978-3-642-13615-3_9 |isbn=978-3-642-13614-6 }}</ref> In anoxic or methanogenic environments such as wetlands, swamps, paddy fields, landfills, digestive tract of [[ruminant]]s, and anerobic digesters syntrophy is employed to overcome the energy constraints as the reactions in these environments proceed close to [[thermodynamic equilibrium]].<ref name="Morris_2013" /><ref name="Worm_2010" /><ref name="Jackson_2002">{{cite journal | vauthors = Jackson BE, McInerney MJ | title = Anaerobic microbial metabolism can proceed close to thermodynamic limits | journal = Nature | volume = 415 | issue = 6870 | pages = 454–456 | date = January 2002 | pmid = 11807560 | doi = 10.1038/415454a | s2cid = 9126984 | bibcode = 2002Natur.415..454J }}</ref>

=== Mechanism of microbial syntrophy === The main mechanism of syntrophy is removing the metabolic end products of one species so as to create an energetically favorable environment for another species.<ref name="Jackson_2002" /> This obligate metabolic cooperation is required to facilitate the degradation of complex organic substrates under anaerobic conditions. Complex organic compounds such as ethanol, [[propionate]], [[butyrate]], and [[Lactic acid|lactate]] cannot be directly used as substrates for [[methanogenesis]] by methanogens.<ref name="Morris_2013" /> On the other hand, [[fermentation]] of these organic compounds cannot occur in fermenting microorganisms unless the hydrogen concentration is reduced to a low level by the methanogens. The key mechanism that ensures the success of syntrophy is interspecies electron transfer.<ref name="Zhang_2019">{{Cite journal |vauthors = Zhang M, Zang L |date=2019 |title=A review of interspecies electron transfer in anaerobic digestion |journal=IOP Conf. Ser: Earth Environ|volume=310 |issue=4 |article-number=042026 |doi=10.1088/1755-1315/310/4/042026 |bibcode=2019E&ES..310d2026Z |s2cid=202886264 |doi-access=free }}</ref> The interspecies electron transfer can be carried out via three ways: [[interspecies hydrogen transfer]], interspecies formate transfer and interspecies direct electron transfer.<ref name="Zhang_2019" /><ref>{{cite journal | vauthors = Rotaru AE, Shrestha PM, Liu F, Ueki T, Nevin K, Summers ZM, Lovley DR | title = Interspecies electron transfer via hydrogen and formate rather than direct electrical connections in cocultures of Pelobacter carbinolicus and Geobacter sulfurreducens | journal = Applied and Environmental Microbiology | volume = 78 | issue = 21 | pages = 7645–7651 | date = November 2012 | pmid = 22923399 | pmc = 3485699 | doi = 10.1128/AEM.01946-12 | bibcode = 2012ApEnM..78.7645R }}</ref> [[Reverse electron flow|Reverse electron transport]] is prominent in syntrophic metabolism.<ref name="McInerney_2019" />

The metabolic reactions and the energy involved for syntrophic degradation with H₂ consumption:<ref name="Zhang_2023">{{Cite journal | vauthors = Zhang Y, Li C, Yuan Z, Wang R, Angelidaki I, Zhu G |date=2023-01-15 |title=Syntrophy mechanism, microbial population, and process optimization for volatile fatty acids metabolism in anaerobic digestion |journal=Chemical Engineering Journal |language=en |volume=452 |article-number=139137 |doi=10.1016/j.cej.2022.139137 |bibcode=2023ChEnJ.45239137Z |s2cid=252205776 |issn=1385-8947|url=https://backend.orbit.dtu.dk/ws/files/294418934/Manuscript_Yao_Zhang.pdf }}</ref>

A classical syntrophic relationship can be illustrated by the activity of ''Methanobacillus omelianskii''. It was isolated several times from anaerobic sediments and sewage sludge and was regarded as a pure culture of an anaerobe converting ethanol to acetate and methane. In fact, however, the culture turned out to consist of a methanogenic archaeon "organism M.o.H" and a Gram-negative Bacterium "Organism S" which involves the oxidization of [[ethanol]] into acetate and [[methane]] mediated by [[interspecies hydrogen transfer]]. Individuals of organism S are observed as obligate [[anaerobic bacteria]] that use ethanol as an [[electron donor]], whereas M.o.H are [[methanogens]] that oxidize hydrogen gas to produce methane.<ref name="Zhang_2023" /><ref>{{cite journal | vauthors = Wrede C, Dreier A, Kokoschka S, Hoppert M | title = Archaea in symbioses | journal = Archaea | volume = 2012 | article-number = 596846 | date = 2012 | pmid = 23326206 | pmc = 3544247 | doi = 10.1155/2012/596846 | doi-access = free }}</ref><ref name="Morris_2013"/>

'''Organism S:''' 2 Ethanol + 2 H₂O → 2 Acetate⁻ + 2 H⁺ + 4 H₂ (ΔG°' = +9.6 kJ per reaction)

'''Strain M.o.H.:''' 4 H₂ + CO₂ → Methane + 2 H₂O (ΔG°' = -131 kJ per reaction)

'''Co-culture:''' 2 Ethanol + CO₂ → 2 Acetate⁻ + 2 H⁺ + Methane (ΔG°' = -113 kJ per reaction)

The oxidization of ethanol by organism S is made possible thanks to the methanogen M.o.H, which consumes the hydrogen produced by organism S, by turning the positive [[Gibbs free energy]] into negative Gibbs free energy. This situation favors growth of organism S and also provides energy for methanogens by consuming hydrogen. Down the line, acetate accumulation is also prevented by similar syntrophic relationship.<ref name="Zhang_2023" /> Syntrophic degradation of substrates like butyrate and benzoate can also happen without hydrogen consumption.<ref name="Jackson_2002"/>

An example of propionate and butyrate degradation with interspecies formate transfer carried out by the mutual system of ''[[Syntrophomonas wolfei]]'' and ''Methanobacterium formicicum'':<ref name="Zhang_2019" />

: Propionate + 2H₂O + 2CO₂ → Acetate⁻ + 3Formate⁻ + 3H⁺ (ΔG°'=+65.3 kJ/mol)

:Butyrate + 2H2O + 2CO₂ → 2Acetate- + 3Formate- + 3H⁺ (ΔG°'=+38.5 kJ/mol)

Direct interspecies electron transfer (DIET) which involves electron transfer without any electron carrier such as H₂ or formate was reported in the co-culture system of ''Geobacter mettalireducens'' and [[Methanosaeta|''Methanosaeto'']] or ''[[Methanosarcina]]''<ref name="Zhang_2019" /><ref name="pmid26337845">{{cite book | vauthors = Dubé CD, Guiot SR | chapter = Direct Interspecies Electron Transfer in Anaerobic Digestion: A Review | series = Advances in Biochemical Engineering/Biotechnology | title = Biogas Science and Technology | volume = 151 | pages = 101–15 | date = 2015 | pmid = 26337845 | doi = 10.1007/978-3-319-21993-6_4 | isbn = 978-3-319-21992-9 }}</ref>

== Examples ==

=== In ruminants === The defining feature of [[ruminant]]s, such as cows and goats, is a stomach called a [[rumen]].<ref>{{Cite web |work = AnimalSmart.org |title=What's a Rumen |url=https://animalsmart.org/species/what%27s-a-rumen- |access-date=2022-11-21 |language=en}}</ref> The rumen contains billions of microbes, many of which are syntrophic.<ref name="Worm_2010" /><ref name="Ng_2016">{{cite journal | vauthors = Ng F, Kittelmann S, Patchett ML, Attwood GT, Janssen PH, Rakonjac J, Gagic D | title = An adhesin from hydrogen-utilizing rumen methanogen Methanobrevibacter ruminantium M1 binds a broad range of hydrogen-producing microorganisms | journal = Environmental Microbiology | volume = 18 | issue = 9 | pages = 3010–3021 | date = September 2016 | pmid = 26643468 | doi = 10.1111/1462-2920.13155 | doi-access = free | bibcode = 2016EnvMi..18.3010N }}</ref> Some anaerobic fermenting microbes in the rumen (and other gastrointestinal tracts) are capable of degrading organic matter to [[short chain fatty acids]], and hydrogen.<ref name="Worm_2010" /><ref name="Morris_2013" /> The accumulating [[hydrogen]] inhibits the microbe's ability to continue degrading organic matter, but the presence of syntrophic hydrogen-consuming microbes allows continued growth by metabolizing the waste products.<ref name="Ng_2016" /> In addition, fermentative bacteria gain maximum energy yield when [[protons]] are used as electron acceptor with concurrent [[Hydrogen|H]]₂ production. Hydrogen-consuming organisms include [[methanogens]], sulfate-reducers, [[acetogens]], and others.<ref>{{Cite web | vauthors = Sapkota A |date=2022-07-12 |title=Syntrophism or Syntrophy Interaction- Definition, Examples |url=https://thebiologynotes.com/syntrophism-or-syntrophy/ |access-date=2022-11-21 |website=The Biology Notes |language=en-US}}</ref>

Some fermentation products, such as [[fatty acids]] longer than two carbon atoms, alcohols longer than one carbon atom, and branched chain and aromatic fatty acids, cannot directly be used in [[methanogenesis]].<ref>{{Cite journal | vauthors = Kang D, Saha S, Kurade MB, Basak B, Ha G, Jeon B, Lee SS, Kim JR | display-authors = 6 |date= July 2021 |title=Dual-stage pulse-feed operation enhanced methanation of lipidic waste during co-digestion using acclimatized consortia |journal=Renewable and Sustainable Energy Reviews |language=en |volume=145 |article-number=111096 |doi=10.1016/j.rser.2021.111096 | bibcode = 2021RSERv.14511096K |s2cid=234830362 |issn=1364-0321}}</ref> In [[acetogenesis]] processes, these products are oxidized to [[acetate]] and H₂ by obligated proton reducing bacteria in syntrophic relationship with methanogenic [[archaea]] as low H₂ partial pressure is essential for acetogenic reactions to be thermodynamically favorable (ΔG < 0).<ref name="Stams_2006">{{cite journal | vauthors = Stams AJ, de Bok FA, Plugge CM, van Eekert MH, Dolfing J, Schraa G | title = Exocellular electron transfer in anaerobic microbial communities | journal = Environmental Microbiology | volume = 8 | issue = 3 | pages = 371–382 | date = March 2006 | pmid = 16478444 | doi = 10.1111/j.1462-2920.2006.00989.x | bibcode = 2006EnvMi...8..371S }}</ref>

=== Biodegradation of pollutants ===

Syntrophic microbial [[food webs]] play an integral role in bioremediation especially in environments contaminated with crude oil and petrol. Environmental contamination with [[Petroleum|oil]] is of high ecological importance and can be effectively mediated through syntrophic degradation by complete mineralization of [[alkane]], [[aliphatic]] and [[hydrocarbon]] chains.<ref name="Callaghan_2012"/><ref name="Ferry_1976">{{cite journal | vauthors = Ferry JG, Wolfe RS | title = Anaerobic degradation of benzoate to methane by a microbial consortium | journal = Archives of Microbiology | volume = 107 | issue = 1 | pages = 33–40 | date = February 1976 | pmid = 1252087 | doi = 10.1007/BF00427864 | bibcode = 1976ArMic.107...33F | s2cid = 31426072 }}</ref> The hydrocarbons of the oil are broken down after activation by [[fumarate]], a chemical compound that is regenerated by other microorganisms.<ref name="Callaghan_2012">{{cite journal | vauthors = Callaghan AV, Morris BE, Pereira IA, McInerney MJ, Austin RN, Groves JT, Kukor JJ, Suflita JM, Young LY, Zylstra GJ, Wawrik B | display-authors = 6 | title = The genome sequence of Desulfatibacillum alkenivorans AK-01: a blueprint for anaerobic alkane oxidation | journal = Environmental Microbiology | volume = 14 | issue = 1 | pages = 101–113 | date = January 2012 | pmid = 21651686 | doi = 10.1111/j.1462-2920.2011.02516.x | bibcode = 2012EnvMi..14..101C }}</ref> Without regeneration, the microbes degrading the oil would eventually run out of fumarate and the process would cease. This breakdown is crucial in the processes of [[bioremediation]] and global carbon cycling.<ref name="Callaghan_2012" />

Syntrophic microbial communities are key players in the breakdown of [[aromatic compounds]], which are common pollutants.<ref name="Ferry_1976" /> The degradation of aromatic [[Benzoic acid|benzoate]] to [[methane]] produces intermediate compounds such as [[formate]], [[acetate]], {{CO2|link=yes}} and H₂.<ref name="Ferry_1976" /> The buildup of these products makes benzoate degradation thermodynamically unfavorable. These intermediates can be metabolized syntrophically by [[methanogens]] and makes the degradation process thermodynamically favorable<ref name="Ferry_1976" />

=== Degradation of amino acids === Studies have shown that bacterial degradation of [[amino acids]] can be significantly enhanced through the process of syntrophy.<ref name="Zindel_1988">{{Cite journal | vauthors = Zindel U, Freudenberg W, Rieth M, Andreesen JR, Schnell J, Widdel F |date= July 1988 |title=Eubacterium acidaminophilum sp. nov., a versatile amino acid-degrading anaerobe producing or utilizing H2 or formate |journal=Archives of Microbiology |language=en |volume=150 |issue=3 |pages=254–266 |doi=10.1007/BF00407789 |bibcode= 1988ArMic.150..254Z |issn=0302-8933 |s2cid=34824309}}</ref> Microbes growing poorly on amino acid substrates [[alanine]], [[aspartate]], [[serine]], [[leucine]], [[valine]], and [[glycine]] can have their rate of growth dramatically increased by syntrophic H₂ scavengers. These scavengers, like ''[[Methanospirillum]] ''and'' [[Acetobacterium]],'' metabolize the H₂ waste produced during amino acid breakdown, preventing a toxic build-up.<ref name="Zindel_1988" /> Another way to improve amino acid breakdown is through interspecies [[electron transfer]] mediated by formate. Species like ''[[Desulfovibrio]]'' employ this method.<ref name="Zindel_1988" /> Amino acid fermenting anaerobes such as ''[[Clostridium]]'' species, ''Peptostreptococcus asacchaarolyticus'', ''Acidaminococcus fermentans'' were known to breakdown amino acids like [[Glutamic acid|glutamate]] with the help of hydrogen scavenging methanogenic partners without going through the usual [[Stickland fermentation]] pathway<ref name="Worm_2010" /><ref name="Zindel_1988" />

=== Anaerobic digestion === Effective syntrophic cooperation between propionate oxidizing bacteria, acetate oxidizing bacteria and H₂/acetate consuming methanogens is necessary to successfully carryout anaerobic digestion to produce biomethane<ref name="Kamagata_2015" /><ref name="Zhang_2023" />

== Syntrophic theories of eukaryogenesis == Many [[Symbiogenesis|symbiogenetic]] models of [[eukaryogenesis]] propose that the first [[Eukaryote|eukaryotic]] cells were derived from [[Endosymbiont|endosymbiosis]] facilitated by microbial syntrophy between [[Prokaryote|prokaryotic]] cells. Most of these models involve an [[Archaea|archaeon]] and an [[Alphaproteobacteria|alphaproteobacterium]], where the dependence of the [[Archaea|archaeon]] on the [[Alphaproteobacteria|alphaproteobacterium]] leads the former to engulf the latter, the [[Alphaproteobacteria|alphaproteobacterium]] then eventually becoming the [[Mitochondrion|mitochondria]]. While these models share the concept of syntrophic interaction as a key driver of [[Endosymbiont|endosymbiosis]], they often differ on the exact nature of the metabolic interactions involved and the mechanisms by which [[eukaryogenesis]] occurred.

=== Hydrogen hypothesis === In 1998, William F. Martin and Miklós Müller introduced the hydrogen hypothesis, proposing that [[Eukaryote|eukaryotes]] arose from syntrophic associations based on the transfer of H₂.<ref name=":12">{{Cite journal |last1=Martin |first1=William |last2=Müller |first2=Miklós |date=March 1998 |title=The hydrogen hypothesis for the first eukaryote |url=https://www.nature.com/articles/32096 |journal=Nature |language=en |volume=392 |issue=6671 |pages=37–41 |doi=10.1038/32096 |pmid=9510246 |bibcode=1998Natur.392...37M |issn=1476-4687|url-access=subscription }}</ref> In this model, an syntrophic association arose where a anaerobic [[Autotroph|autotrophic]] [[Methanogenesis|methanogenic]] [[Archaea|archaeon]] was dependent on the H₂ made as a byproduct of [[anaerobic respiration]] by a facultatively anaerobic [[Alphaproteobacteria|alphaproteobacterium]].<ref name=":12" /> This syntrophy led the [[Alphaproteobacteria|alphaproteobacterium]] to become an [[endosymbiont]] of the [[Archaea|archaeon]], serving as the precursor to the [[Mitochondrion|mitochondria]].

=== Dennis Searcy model === Dennis Searcy proposed that the precursors to [[Mitochondrion|mitochondria]] were [[Parasitism|parasitic]] [[bacteria]] that developed a syntrophy with their hosts based upon the transfer of organic acids, H₂ transfer, and the reciprocal exchange of sulfur compounds.<ref>{{Cite journal |last=Searcy |first=Dennis G. |date=August 2003 |title=Metabolic integration during the evolutionary origin of mitochondria |url=https://www.nature.com/articles/7290168 |journal=Cell Research |language=en |volume=13 |issue=4 |pages=229–238 |doi=10.1038/sj.cr.7290168 |pmid=12974613 |issn=1748-7838}}</ref>

=== Reverse flow model === The reverse flow model was created based on the metabolic analysis of [[Asgard (Archaea)|Asgard archaea]], which is thought to be the kingdom from which [[Eukaryote|eukaryotes]] emerged.<ref name=":22">{{Cite journal |last1=Spang |first1=Anja |last2=Stairs |first2=Courtney W. |last3=Dombrowski |first3=Nina |last4=Eme |first4=Laura |last5=Lombard |first5=Jonathan |last6=Caceres |first6=Eva F. |last7=Greening |first7=Chris |last8=Baker |first8=Brett J. |last9=Ettema |first9=Thijs J. G. |date=July 2019 |title=Proposal of the reverse flow model for the origin of the eukaryotic cell based on comparative analyses of Asgard archaeal metabolism |url=https://www.nature.com/articles/s41564-019-0406-9 |journal=Nature Microbiology |language=en |volume=4 |issue=7 |pages=1138–1148 |doi=10.1038/s41564-019-0406-9 |pmid=30936488 |issn=2058-5276}}</ref><ref>{{Cite journal |last1=Zaremba-Niedzwiedzka |first1=Katarzyna |last2=Caceres |first2=Eva F. |last3=Saw |first3=Jimmy H. |last4=Bäckström |first4=Disa |last5=Juzokaite |first5=Lina |last6=Vancaester |first6=Emmelien |last7=Seitz |first7=Kiley W. |last8=Anantharaman |first8=Karthik |last9=Starnawski |first9=Piotr |last10=Kjeldsen |first10=Kasper U. |last11=Stott |first11=Matthew B. |last12=Nunoura |first12=Takuro |last13=Banfield |first13=Jillian F. |last14=Schramm |first14=Andreas |last15=Baker |first15=Brett J. |date=January 2017 |title=Asgard archaea illuminate the origin of eukaryotic cellular complexity |url=https://www.nature.com/articles/nature21031 |journal=Nature |language=en |volume=541 |issue=7637 |pages=353–358 |doi=10.1038/nature21031 |pmid=28077874 |bibcode=2017Natur.541..353Z |osti=1580084 |issn=1476-4687}}</ref><ref>{{Cite journal |last1=Spang |first1=Anja |last2=Saw |first2=Jimmy H. |last3=Jørgensen |first3=Steffen L. |last4=Zaremba-Niedzwiedzka |first4=Katarzyna |last5=Martijn |first5=Joran |last6=Lind |first6=Anders E. |last7=van Eijk |first7=Roel |last8=Schleper |first8=Christa |last9=Guy |first9=Lionel |last10=Ettema |first10=Thijs J. G. |date=May 2015 |title=Complex archaea that bridge the gap between prokaryotes and eukaryotes |journal=Nature |language=en |volume=521 |issue=7551 |pages=173–179 |doi=10.1038/nature14447 |pmid=25945739 |pmc=4444528 |bibcode=2015Natur.521..173S |issn=1476-4687}}</ref> This model proposes that a syntrophic association arose where anaerobic ancestral [[Asgard (Archaea)|Asgard archaea]] generated and provided reducing equivalents that facultative anaerobic [[alphaproteobacteria]] used in the form of H₂, small reduced compounds, or by direct [[electron]] transfer.<ref name=":22" />

=== Entangle-Engulf-Endogenize model === The Entangle-Engulf-Endogenize (E3) model was created in 2020 based on the isolation of syntrophic [[archaea]] from deep sea marine sediment.<ref name=":3">{{Cite journal |last1=Imachi |first1=Hiroyuki |last2=Nobu |first2=Masaru K. |last3=Nakahara |first3=Nozomi |last4=Morono |first4=Yuki |last5=Ogawara |first5=Miyuki |last6=Takaki |first6=Yoshihiro |last7=Takano |first7=Yoshinori |last8=Uematsu |first8=Katsuyuki |last9=Ikuta |first9=Tetsuro |last10=Ito |first10=Motoo |last11=Matsui |first11=Yohei |last12=Miyazaki |first12=Masayuki |last13=Murata |first13=Kazuyoshi |last14=Saito |first14=Yumi |last15=Sakai |first15=Sanae |date=January 2020 |title=Isolation of an archaeon at the prokaryote–eukaryote interface |journal=Nature |language=en |volume=577 |issue=7791 |pages=519–525 |doi=10.1038/s41586-019-1916-6 |issn=1476-4687 |pmc=7015854 |pmid=31942073|bibcode=2020Natur.577..519I }}</ref> Unlike most other symbiogenetic models, the E3 model involves three separate types of microbes: a [[Fermentation|fermentative]] [[Archaea|archaeon]], a facultatively aerobic [[organotroph]] (which was acts as the precursor of the mitochondria), and [[sulfur-reducing bacteria]] (SRB).<ref name=":3" /> This model proposes that, originally, the [[Fermentation|fermentative]] [[Archaea|archaeon]] may have degraded [[Amino acid|amino acids]] via syntrophic association with [[Sulfur-reducing bacteria|SRB]] and the facultatively aerobic [[organotroph]].<ref name=":3" /> As [[oxygen]] levels began to rise, however, the interaction with the facultatively aerobic [[organotroph]] (which is thought to have made the [[Archaea|archaeon]] more aerotolerant) became stronger became stronger until it was engulfed (a process facilitated by syntrophic interaction with [[Sulfur-reducing bacteria|SRB]]).<ref name=":3" /> Additionally, the E3 model suggests that, instead of [[Phagocytosis|phagocytizing]] the facultatively aerobic [[organotroph]], the [[Archaea|archaeon]] used extracellular structures to enhance interactions and engulf the facultatively aerobic [[organotroph]].<ref name=":3" />

=== Syntrophy hypothesis === The syntrophy hypothesis was proposed in 2001 by researchers Purificación López-García and David Moreira before being refined in 2020 by the same researchers.<ref>{{Citation |last1=LóPez-García |first1=P. |title=The Syntrophy Hypothesis for the Origin of Eukaryotes |date=2002 |work=Symbiosis: Mechanisms and Model Systems |pages=131–146 |editor-last=Seckbach |editor-first=Joseph |url=https://link.springer.com/chapter/10.1007/0-306-48173-1_8 |access-date=2025-05-01 |place=Dordrecht |publisher=Springer Netherlands |language=en |doi=10.1007/0-306-48173-1_8 |isbn=978-0-306-48173-4 |last2=Moreira |first2=D.|url-access=subscription }}</ref><ref name=":4">{{Cite journal |last1=López-García |first1=Purificación |last2=Moreira |first2=David |date=May 2020 |title=The Syntrophy hypothesis for the origin of eukaryotes revisited |url=https://www.nature.com/articles/s41564-020-0710-4 |journal=Nature Microbiology |language=en |volume=5 |issue=5 |pages=655–667 |doi=10.1038/s41564-020-0710-4 |pmid=32341569 |issn=2058-5276}}</ref> Similarly to the E3 model, the syntrophy hypothesis suggests that [[eukaryogenesis]] involved three different types of microbes: a complex sulfate-reducing [[Myxococcota|deltaproteobacterium]] (the precursor to the [[cytoplasm]]), an H₂-producing [[Asgard (Archaea)|Asgard archaeon]] (the precursor to the [[Cell nucleus|nucleus]]), and a facultatively aerobic sulfide-oxidizing [[Alphaproteobacteria|alphaproteobacterium]] (the precursor to [[Mitochondrion|mitochondria]]).<ref name=":4" /> In this model, the [[Myxococcota|deltaproteobacteria]] forms syntrophic associations with both the [[Asgard (Archaea)|Asgard archaeon]] (based on the transfer of H₂) and the [[Alphaproteobacteria|alphaproteobacterium]] (based on the redox of sulfur), leading both to become [[Endosymbiont|endosymbionts]] of the [[Myxococcota|deltaproteobacteria]].<ref name=":4" /> In this now obligatory [[symbiosis]], organic compounds were degraded in the [[Periplasm|periplasmic space]] of the [[Myxococcota|deltaproteobacteria]] before being moved to the [[Archaea|archaeon]] for further degradation.<ref name=":4" /> This interaction drove the [[periplasm]] to develop and expand in close proximity with the [[Archaea|archaeon]] to facilitate molecular exchange, resulting in an [[endomembrane system]], transport channels, and the loss of the [[Archaea|archaeal]] membrane.<ref name=":4" /> Ultimately, the archaeon became the nucleus while the periplasmic endomembrane system became the endoplasmic reticulum.<ref name=":4" /> Meanwhile, the consortium lost the metabolic capability for [[Bacteria|bacterial]] sulfate reduction and [[Archaea|archaeal]] energy [[metabolism]] as it became more reliant on aerobic [[Cellular respiration|respiration]] performed by the [[Alphaproteobacteria|alphaproteobacterium]] which, ultimately, became the [[mitochondrion]].<ref name=":4" />

== Examples of syntrophic organisms == * ''[[Syntrophomonas wolfei]]'' is a gram-negative, anaerobic, fatty-acid oxidizing bacterium that forms syntrophic associations with H₂-using bacteria.<ref>{{cite journal | vauthors = McInerney MJ, Bryant MP, Hespell RB, Costerton JW | title = Syntrophomonas wolfei gen. nov. sp. nov., an Anaerobic, Syntrophic, Fatty Acid-Oxidizing Bacterium | journal = Applied and Environmental Microbiology | volume = 41 | issue = 4 | pages = 1029–1039 | date = April 1981 | pmid = 16345745 | pmc = 243852 | doi = 10.1128/aem.41.4.1029-1039.1981 | bibcode = 1981ApEnM..41.1029M }}</ref> * ''[[Syntrophobacter fumaroxidans]]'' is a gram-negative anaerobic bacterium that can oxidize propionate in pure cultures or in syntrophic association with ''Methanospirillum hungateii.''<ref name="Schink_2013" /><ref>{{Cite journal |last1=HARMSEN |first1=H. J. M. |last2=VAN KUIJK |first2=B. L. M. |last3=PLUGGE |first3=C. M. |last4=AKKERMANS |first4=A. D. L. |last5=DE VOS |first5=W. M. |last6=STAMS |first6=A. J. M. |date=1998-10-01 |title=Syntrophobacter fumaroxidans sp. nov., a syntrophic propionate-degrading sulfate-reducing bacterium |journal=International Journal of Systematic Bacteriology |volume=48 |issue=4 |pages=1383–1387 |doi=10.1099/00207713-48-4-1383 |pmid=9828440 |issn=0020-7713}}</ref> * ''[[Pelotomaculum thermopropionicum]]'' is a thermophilic, anaerobic, syntrophic propionate-oxidizing bacterium that, in co-culture with ''Methanothermobacter thermautotrophicus'', can grow on propionate, ethanol, lactate, 1-butanol, 1-pentanol, 1,3-propanediol, 1-propanol, and ethylene glycol.<ref name="Schink_2013" /><ref>{{Cite journal |last1=Imachi |first1=Hiroyuki |last2=Sekiguchi |first2=Yuji |last3=Kamagata |first3=Yoichi |last4=Hanada |first4=Satoshi |last5=Ohashi |first5=Akiyoshi |last6=Harada |first6=Hideki |date=2002-09-01 |title=Pelotomaculum thermopropionicum gen. nov., sp. nov., an anaerobic, thermophilic, syntrophic propionate-oxidizing bacterium. |journal=International Journal of Systematic and Evolutionary Microbiology |volume=52 |issue=5 |pages=1729–1735 |doi=10.1099/00207713-52-5-1729 |pmid=12361280 |issn=1466-5026}}</ref> * ''[[Syntrophus aciditrophicus]]'' is a gram-negative, obligately anaerobic, nonmotile, rod-shaped bacterium that, in syntrophic association with hydrogen/formate-using methanogens or sulfate reducers, degrades benzoate and fatty acids.<ref name="Jackson_2002" /><ref>{{Cite journal |last1=Jackson |first1=Bradley E. |last2=McInerney |first2=Michael J. |date=January 2002 |title=Anaerobic microbial metabolism can proceed close to thermodynamic limits |journal=Nature |volume=415 |issue=6870 |pages=454–456 |doi=10.1038/415454a |pmid=11807560 |bibcode=2002Natur.415..454J |issn=0028-0836}}</ref><ref>{{Cite journal |last1=Jackson |first1=Bradley E. |last2=Bhupathiraju |first2=V. K. |last3=Tanner |first3=Ralph S. |last4=Woese |first4=Carl R. |last5=McInerney |first5=M. J. |date=1999-01-14 |title=Syntrophus aciditrophicus sp. nov., a new anaerobic bacterium that degrades fatty acids and benzoate in syntrophic association with hydrogen-using microorganisms |journal=Archives of Microbiology |volume=171 |issue=2 |pages=107–114 |doi=10.1007/s002030050685 |pmid=9914307 |bibcode=1999ArMic.171..107J |issn=0302-8933}}</ref> * ''[[Syntrophus buswellii]]'' is a gram-negative, anaerobic, motile, rod-shaped bacterium that, in syntrophic association with H₂-using bacteria, degrades benzoate.<ref name="Worm_2010" /><ref>{{Cite journal |last1=Mountfort |first1=Douglas O. |last2=Bryant |first2=Marvin P. |date=1982 |title=Isolation and characterization of an anaerobic syntrophic benzoate-degrading bacterium from sewage sludge |journal=Archives of Microbiology |volume=133 |issue=4 |pages=249–256 |doi=10.1007/bf00521285 |bibcode=1982ArMic.133..249M |issn=0302-8933}}</ref> * ''Syntrophus gentianae'' is a obligately anaerobic bacterium that ferments benzoate in syntrophic association with H₂-using bacteria.<ref>{{cite journal | vauthors = Schöcke L, Schink B | title = Membrane-bound proton-translocating pyrophosphatase of Syntrophus gentianae, a syntrophically benzoate-degrading fermenting bacterium | journal = European Journal of Biochemistry | volume = 256 | issue = 3 | pages = 589–594 | date = September 1998 | pmid = 9780235 | doi = 10.1046/j.1432-1327.1998.2560589.x | url = http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-59985 }}</ref>

== References == {{Reflist}}

[[Category:Biological interactions]] [[Category:Food chains]]