life Review Insights into Abiotically-Generated Amino Acid Enantiomeric Excesses Found in Meteorites AaronS.Burton1,* ID andEveL.Berger2 ID 1 AstromaterialsResearchandExplorationScience,NASAJohnsonSpaceCenter,Houston,TX77058,USA 2 GeoControlSystems,JacobsJETScontract,NASAJohnsonSpaceCenter,Houston,TX77058,USA; [email protected] * Correspondence:[email protected];Tel.:+1-281-244-2773 (cid:1)(cid:2)(cid:3)(cid:1)(cid:4)(cid:5)(cid:6)(cid:7)(cid:8)(cid:1) (cid:1)(cid:2)(cid:3)(cid:4)(cid:5)(cid:6)(cid:7) Received:27April2018;Accepted:10May2018;Published:12May2018 Abstract: Biologyexhibitshomochirality,inthatonlyoneoftwopossiblemolecularconfigurations (called enantiomers) is used in both proteins and nucleic acids. The origin of this phenomenon is currently unknown, as nearly all known abiotic mechanisms for generating these compounds resultinequal(racemic)mixturesofbothenantiomers. However,analysesofprimitivemeteorites haverevealedthatanumberofaminoacidsofextraterrestrialoriginarepresentinenantiomeric excess,suggestingthattherewasanabioticroutetosynthesizeaminoacidsinanon-racemicmanner. Herewereviewtheaminoacidcontentsofarangeofmeteorites,describemechanismsforaminoacid formationandtheirpotentialtoproduceaminoacidenantiomericexcesses,andidentifyprocesses thatcouldhaveamplifiedenantiomericexcesses. Keywords: aminoacids;chirality;meteorites;homochirality;enantiomer;prebioticchemistry 1. Introduction Aminoacidsarethebuildingblocksofproteins,themolecularmachinesresponsibleforcatalyzing nearlyallchemicalreactionsnecessaryforlife. Theuniversalproteinalphabetconsistsof20amino acids,allofwhichareα-aminoacids,wheretheaminogroupisattachedtothecarbonimmediately adjacenttothecarboxylicacidmoiety(Figure1A).Ofthese20proteinogenicaminoacids,oneisachiral (glycine),andtheother19havechiralcarbonsandcanexistaseitheroftwopossiblestereoisomers (Figure1B),whicharedenotedasenantiomers. Enantiomersofagivenchiralcompoundhaveidentical chemical and physical properties, except for how they interact with other chiral compounds and howtheyinteractwithpolarizedlight. Nevertheless,biologyhasevolvedtouseonlyL-aminoacids (homochirality)intheproductionofgeneticallyencodedproteins. Similarly,biology’sinformational polymers,ribonucleicanddeoxyribonucleicacid,arealsohomochiral,containingonlyD-enantiomers (Figure1C). GiventhephysicalandchemicalequivalenceofD-andL-aminoacids(andsugars),theredoesnot appeartobeanapriorireasonfortheselectionofL-aminoacidsoverD-aminoacids. Indeed,ithas beenshownthatstereoisomersoftheproteinHIVprotease1containingonlyD-aminoacidsoronly L-aminoacidsexhibitidenticalcatalyticproperties,withthesoledifferenceintheiractivitiesbeingan inversioninthestereochemistryofthesubstratesonwhichthesetwoenzymesact[1]. Althoughmost L-proteinshaveevolvedtorecognizeD-sugars,studieshaveshownthatnaturally-occurringL-proteins canalsoacton L-sugars,includingthecatabolismof L-glucose[2],and L-guloseand L-fructose[3]. Thus,theredoesnotappeartobeastrictlinkbetweenaminoacidandsugarchirality. Thisisperhaps notsurprisinggiventhatintheLandDterminologyonlyonechiralcenterisevaluatedtoassignLor D,whereasthepredominantsugarsinbiologycontainmultiplechiralcenters(e.g.,ribose,deoxyribose, glucose,fructose,etc.;Figure1C).Theseobservations,takentogether,suggestthatanyofthefourchiral Life2018,8,14;doi:10.3390/life8020014 www.mdpi.com/journal/life Life2018,8,14 2of21 Life 2018, 8, x 2 of 21 comtobgienthateiro, nsusg(Lg-easmt tihnaot aanciyd osfa tnhde fLo-usru cghairrsa;l Lc-oammbiinnoataicoindss (aL-nadmDin-sou agcaidrss; aDn-da mL-sinuogaarcsi;d Ls-aamndinoD -ascuidgsa rs; andanDd- aDm-siungoarasc;i dDs-aamnidnoL -ascuigdasr asn)dco Du-lsduhgaarvse; asundst aDi-naemdinliofe a.cTidhse aunbdiq Lu-istuygoafrsL)- acmouilndo haacvide ssuinstparinoetedi ns life. The ubiquity of L-amino acids in proteins and D-sugars in nucleic acids and metabolism across andD-sugarsinnucleicacidsandmetabolismacrossalldomainsoflifeprovidesstrongevidencethat all domains of life provides strong evidence that these choices were fixed prior to the Last Universal thesechoiceswerefixedpriortotheLastUniversalCommonAncestor(LUCA).Incontrastwithamino Common Ancestor (LUCA). In contrast with amino acids and sugars, both enantiomers of chiral acidsandsugars,bothenantiomersofchiralphospholipids(amajorcomponentofcellmembranes), phospholipids (a major component of cell membranes), are used in extant biology, with archaea and are used in extant biology, with archaea and bacteria using opposite enantiomers [4]. In this case, bacteria using opposite enantiomers [4]. In this case, selection occurred post-LUCA. While selectionoccurredpost-LUCA.Whilecontemporarybiologytellsuswhichstereochemistrieswere contemporary biology tells us which stereochemistries were ultimately selected for, and provides a ultimatelyselectedfor,andprovidesaconstraintonwhenthatselectionoccurred(priortoLUCA, constraint on when that selection occurred (prior to LUCA, >3.5 Ga for amino acids and sugars, and >3.5Gaforaminoacidsandsugars,andpost-LUCAforphospholipids),analysisofmodernbiology post-LUCA for phospholipids), analysis of modern biology reveals little about how and why L-amino revaecaidlss laitntdle Dab-souugtarhso wwearen dulwtimhyateLl-ya mseilneocteadci dosvearn dtheDi-rs uregsapresctwiveer eenualntitmioamteelrys, sneeleccetsesditaotivnegr athne ir resapletecrtnivaetiveen aanptpioromacehrs. ,necessitatinganalternativeapproach. Figure 1. Structural drawings of amino acids and sugars. (a) A generic α-amino acid, where the amino Figure1.Structuraldrawingsofaminoacidsandsugars.(a)Agenericα-aminoacid,wheretheamino group is connected to the carbon immediately adjacent to the carboxylic acid. (b) groupisconnectedtothecarbonimmediatelyadjacenttothecarboxylicacid.(b)Stereorepresentations Stereorepresentations of the two enantiomers of a chiral α-amino acid, denoted S and R. (c) Fischer ofthetwoenantiomersofachiralα-aminoacid,denotedSandR.(c)Fischerprojectionsdenoting projections denoting chirality of a chiral α-amino acid and sugar (chiral carbons marked with chiralityofachiralα-aminoacidandsugar(chiralcarbonsmarkedwithasterisks),whereLdenotes asterisks), where L denotes left and D denotes right; this naming convention only reflects the first leftandDdenotesright;thisnamingconventiononlyreflectsthefirstchiralcenter. chiral center. Life2018,8,14 3of21 DirectevidenceofprebioticchiralselectiononEarthhasnotyetbeenfound. Itislikelythatany suchrecordsonEarthhavebeenoverwrittenbybillionsofyearsofgeologicalorbiologicalprocessing. However,prebioticchemistrystudiesinthelabhaverevealedthefacilenatureofaminoacidsynthesis under a broad range of plausibly prebiotic conditions. These studies include the spark discharge experiments pioneered by Miller and Urey [5,6], reductive aminations [7], aqueous Strecker-type chemistry [8], and Fischer-Tropsch type syntheses [9,10], etc. Chiral amino acids formed by these processes,however,areformedinequal(racemic)mixturesofL-andD-enantiomers. Hence,although thesereactionscouldhaveprovidedasteadysupplyofaminoacidsfortheoriginsoflife,theydo not appear to be capable of generating chiral excesses of any magnitude, let alone homochirality. Keyoutstandingquestionsintheoriginsoflife,then,includewhatledtothetransitionfromracemic, abioticchemistrytothehomochiralityobservedinbiology,andwhetherthistransitionwasabiological inventionorwasinitiatedbyabioticprocesses. 2. MeteoritesandPrebioticChemistry Althoughsamplesof Earth’snascentprebiotic chemistryareabsent, meteorites, the remnantsof asteroids, comets and planetary bodies that reach the surface of Earth, preserve records of processes andconditionsduringtheoriginandearlyevolutionoftheSolarSystem. Meteoritesincollectionson Earthhavecomefromanincrediblerangeofparentbodies,spanningprimitiveasteroidstoplanet-sized objectsincludingtheMoonandMars.Carbonaceouschondritesinparticularhaverevealedthatcomplex chemistryrelevanttotheoriginsoflifewasoccurringonarangeofplanetarybodiesinearlysolarsystem. Compoundclassesfoundincarbonaceouschondritesthatareofparticularinterestfortheoriginsoflife includecarboxylicacids[11],aminoacids[12],sugarsandsugarderivatives[13],andnucleobases[14]. Evenamongthecarbonaceouschondrites,however,significantvariationsintheabundancesanddiversities ofcompoundshavebeenobserved,revealinganinterplaybetweentheinorganicmeteoriteparentbody material,thepoolofavailablereactants(e.g.,ammonia,hydrogencyanide,aldehydesandketones),and secondarygeologicalprocessessuchasaqueousalterationandthermalalteration[15–17]. Thecarbonaceouschondriteshavebeensubdividedintoeightdistinctgroups(CI,CM,CR,CH, CB, CO, CV and CK) that are named after a representative meteorite (e.g., CI denotes Ivuna-like). Carbonaceouschondritesarecomposedofmixturesoffine-grainedsilicatemineralmatrixmaterial, inwhichadditionalcomponentsareembedded(Table1). Theseinclude: solidironandiron/nickel metal;sulfideminerals;refractoryphasessuchascalciumaluminuminclusions(CAIs)andamoeboid olivineaggregates(AOAs);andchondrules,amongthefirstbitsofmattertocondenseintothesolid phaseinoursolarnebula. Thepresenceofchondrulesdistinguishescarbonaceousandotherchondrites fromlessprimitivepartiallyorcompletelydifferentiatedmeteorites.Carbonaceouschondritegroupings arebasedonfactorssuchasbulkrockcomposition(e.g.,enrichmentsordepletionsofelementsrelativeto thesolarphotosphere;ratiosofreducedtooxidizediron;ratiosofrefractoryandvolatileelements,such asAl/Znvs.Al/Mn),texture,mineralogy,andmineralcompositions.Oxygenisotopecompositionsare alsousedtoclassifymeteorites,althoughthisislessdiagnosticforcarbonaceouschondrites,asoxygen isotopecompositionsofsomecarbonaceouschondritegroupsoverlap. Secondaryprocessessuchas aqueousalterationandthermalmetamorphismarecapturedbypetrologicsub-typing. Carbonaceous chondritesareassignedanumberfrom1–6,whereatype3.0meteoriteexperiencedminimalparent bodyprocessingafteraccretion,types1to<3experiencedincreasingaqueousalteration,andtypes>3 to6experiencedincreasingthermalalteration[18–26]. Forallcarbonaceouschondritegroups,only asubsetofthetotalpetrologictypesisobserved(e.g.,forCRchondrites,samplesfoundtodateare of types 1–3; for CK chondrites known samples are of types 3–6), indicating the parent bodies of thesemeteoritespredominantlyexperiencedeitheraqueousalterationorthermalalteration. Water isakeysolventformanyreactionsofprebioticinterest,butinitial(post-accretion)watercontentsof meteoriteshaveprovenchallengingtotightlyconstrain. However,thegeneralconsensusisthatmostof thecarbonaceouschondritegroupshadwater-to-rockratioslessthan0.5:1[27,28],andthataqueous alterationinmostmeteoritesoccurredattemperaturesbetween0◦Cand150◦C. Life 2018, 8, x 4 of 21 Table 1. Properties of carbonaceous chondrite meteorite groups, including: matrix abundances, chondrule abundances and sizes, refractory component abundances, metallic Fe and Ni abundances, Life2018,8,14 4of21 average olivine compositions, and refractory lithophile element abundances. The carbonaceous chondrite meteorite groups are arranged from left to right (CI to CB) in order of decreasing bulk rock oxidation. Data were compiled from and the table modeled after Brearley and Jones [29], Wesiberg et Table 1. Properties of carbonaceous chondrite meteorite groups, including: matrix abundances, al. [30], Scott and Krot [31], and Scott [32]. Life 2018, 8, x chondruleabundancesandsizes,refractorycomponentabundances,metallicF4e oafn 2d1 Niabundances, CI CM CK CV COa veragCeR olivinCeHc omposCitBi ons, and refractory lithophile element abundances. The carbonaceous Petrologic type 1 1–2 Tab3le–6 1. Pr2o–p3 erties3 of car1b–o3 naceou3s chondr3it e meteorite groups, including: matrix abundances, chondrite meteorite groups are arranged from left to right (CI to CB) in order of decreasing bulk Chondrule abundance (vol. %) ≪1 † 20 ‡ 15 45 40–48 50–60 ~70 20–40 Matrix abundance (vol. %) >99 † 70 ‡ chon7d5r ule ab4u0 nda3n0c–e3rLs4oi fcae kn20d31o0 8x–s, 5ii8zd0, exas t,i orenf.r5a cDtoartay cwo<em5r epocnoemnpt ialbedunfdroamnceasn, dmethtaellitca bFlee amndo dNeil eadbuanfdtearnBcerse,a rley and Jones4 [o2f 92]1, Refractory abundance ⧺ (vol. %) ≪1 5 avera4g e oliv1i0n e com13Wp oessiitbioe0.rn5g s,e taanld.0[ 3.1r0e ]f,raScctoot<rty0a. 1n ldithKorpohti[l3e1 ]e,laenmdeSnct oattb[u3n2d].ances. The carbonaceous Metal (Fe, Ni) abundance (vol. %) ≪1 0.1 chon≪d1r ite m0e–t5e orite1 –g5r oupTs5 a–ab8r lee a 1r.r aPn2rg0o epder ftireosm6 0o –fl8 e0cf at rtboo rniagcheto u(Cs Ic thoo CndBr)i tien moredteeorr iotfe dgercoruepass, iningc lbuudlikn gr:o cmka trix abundances, Avg. chondrule diameter (mm) n.a. 0.3 0.7–0.8 1.0 0.15 c0h.o7 ndru0l.e0 2a–b0u.0n9d an0ce.2s– 1a0n d sizes, refractory component abundances, metallic Fe and Ni abundances, oxidation. Data were compiled from and the table moCdIeled afCteMr BrearleCyK and JoCnVes [29], CWOesibergC eRt CH CB Olivine composition average olivine compositions, and refractory lithophile element abundances. The carbonaceous -(mol % Fe2SiO4; range) * * al. [<310–4]7, Scott *a nd Kr*o t [31]c,Ph ae ontnrddo lrSoitcgeoi< cmt1t–t ey3[t36pe 2eo]r.i te g2r–o3u ps are1 arrange1d– f2rom left3 t–o6 right (C2I– 3to CB) in3 order of d1–e3creasing bu3lk rock 3 -(mol % Fe2SiO4; mode) 29–33 C hondro1ux–li3ed aabtiuoCnn.dI Da2na ctae w(vCeoMrle. %c3o )mpilCe(cid:28)Kd 1 fr†om aCn2Vd0 t‡he taCbOle m15odeCleRd a4f5ter BrCeHa4r0 l–e4y8 and JCo5B0n– e6s 0[29], We~s7ib0erg et 20–40 Refractory Lithophiles ∦ 1.00 1.15 1.21 1.35 1.13 1.03 1.00 1.0–1.4 † Including chondrule fragments and silicate minerals Pientfreorlroegdi ct oty bpee cMhaotnrdiaxrl.ua [lb3eu0 ]fn,r daS1gac nomtctee na(ntvsdo c1 lK.h–%r2ao n)tg [e3s1 ], a3>n–96d9 S†cott 2[3–7230] .‡ 3 75 1–3 40 33 0–34 330 –50 5 <5 Chondrule abundance (vol. %) ≪1 † 20 ‡ 15 45 40–48 50–60 ~70 20–40 matrix and chondrule abundances to >95 vol. % and <5 vol. %, resRpeefcrtaicvteolryy; a‡ bVuanrdiaabnlcee; ⧺ C(vaollc.iu%m) (cid:28)1CI 5CM 4CK C10V CO1 3 CR 0.5 CH 0.1 CB <0.1 Matrix abundance (vol. %) >99 † 70 ‡ 75 40 30–34 30–50 5 <5 Aluminum Inclusions + Amoeboid Olivine Aggregates; * Highly variable and unequPieltirborloagteicd t;y ∦p Me ean 1 1–2 3–6 2–3 3 1–3 3 3 Refractory abundanceM ⧺e (tvalo(lF. %e,)N i)ab≪un1 dance(v5 ol.%) 4(cid:28) 1 100 .1 13 (cid:28)1 0.5 0–5 0.11 –5 <05.1– 8 20 60–80 Chondrule abundance (vol. %) ≪1 † 20 ‡ 15 45 40–48 50–60 ~70 20–40 ratio refractory lithophiles relative to Mg, normalized to CI chondrites. Metal (Fe, Ni) abundanAcev g(v.oclh. o%nM)d arutrlixe≪ ad1bi uamndeatnecr0e.( 1(mv oml. )%) ≪n1. a.>99 † 0–05. 370 ‡ 1–05. 7–705. 85–8 14.00 3200–0 3.145 306–05–008 .07 5 0.02–0.09<5 0.2–10 Avg. chondrule diameter (mmRe) fractorny. aa.b undan0c.e3 ⧺ (vol. 0%.7) –0.8 ≪1 1.0 5 0.15 4 0.7 10 0.02–103.0 9 00..52 –10 0.1 <0.1 A sufficient number of carbonaceous chondritOesl ivoifn ee accohm pgorsoituiopn a nOMdlie vptianel et(Frcoeo,l mNogip) ioacbs iustnuiodbna-ntcyep (veo lh. a%v) e ≪1 0.1 ≪1 0–5 1–5 5–8 20 60–80 now been analyzed for amino acids for the following-( mcoonl c%lu Fsei2oSniOs 4t; or abneg s-e(a)m feoAllyv% gd. Frcaheow2Sn*nid Or: u4(l1;er) da cinaagmr*eb e)otenr a(mcem<o)1u –s4* 7 n.a. * *0.3 * <01.–74–07.8 1*.0 <1–03.165* 0.27 –3 0.02–0.0<9 1–360.2–10 2–3 chondrites of the same group and petrologic type te-(nmdo lt o% h Faev2Sei Osi4m; miloadr-e (a)m buoln%daFOnelc2ivSei isnO ea 4cn;odmm pododisse itt)rioinb u ti2o9n–s3 3 29–33 1–3 2 31 –3 2 3 of amino acids; (2) within carbonaceous chondrRiteef ragcrtoouryp Ls,i thinopcrheilaessRe ∦es f rianc to-t(rhmyeo1L l. di0%t0he Fgoepr2eShieiOl 1e4o;.s 1rf∦5a n agqeu) eo1u.12s.1 0 0 * 1.13.51 5* 1.131 <.12–147 1.031 .3* 5 1.00*1 .13 1. 0–11.0.43 <1–36 1.00 2–3 1.0–1.4 -(mol % Fe2SiO4; mode) 29–33 1–3 2 3 alteration in the meteorite parent body tend t†o I nreclduudcien gth ceh otontdarl ual†be uIfnnrcadlguamdnicneRengestf crsaoh caoft nonarddymr Lusiiinltlehiocof arpaathcegili medmses ∦in, ntasenraadnl ds 1sini.0lfi0ce artreedm1 .it1no5e rbaels cihn1of.2en1r drerdutloe1 .3bf5re acghmo1ne.1dn3rt us lechf1raa.n0g3gm eesn ts1c.h00a nges1m.0a–t1r.i4x and change the amino acid distribution; (3) carbomnaacterioxu as ncdh ochnodnridterus lcefrh oaombnud †r naIudnqlecaulnuaebcodeuuinsns gdlt yoac n ha>col9ents5ed rtrvoeuod>lel 9. g5f%rrvao gouamln.pe%dsn t<asn5 ad nv<do5 ls. vi%loicl,.a tr%ee ,smrpeienscpeteriacvltesiv liyenl;fy e‡; r‡VreVadar ritaoiab bblleee ;; c⧺h oCCnaadllrccuiiuulemm frA algummeinntusm chIanncgluessi ons+ contain higher abundances of amino acids thaAn ltuhmerinmuamlly I naclltuerseiodn csA a+mr bAooemmbnoaoaictedrebiOoxo uliaidvsn i dOnc ehlcioAhvnoginndgderrer iAgtuealge tegg asrr;boe*uguHnapditsgea;hsn l;cy *e vsH atriogi a>hb9llye5 avvnoadlr.i ua%nb elaqenu adinl i<bd5r auvtneodel.;q %∦uM,i lrieebasrnpaertacettdiivo; e∦rl eyMf;r ae‡ caVtnoar ryialibtlheo; p⧺h Cileaslcrieulmat iveto and (4) thermally-altered meteorites have lowerra taibo urnefdraanctcoersy o lfit hamopiMnhoigl, eanscAo rirdlemulsama taliiinnvzeudedm taot o I snMCtcrlIgouc,ns hnigooo nntrdsem rn+i atdAelesimz.neocdeyb tooi dC OI lcihvionned Argitgerse.g ates; * Highly variable and unequilibrated; ∦ Mean for straight-chain amino acids where the amino group is on the carbon fraarttiho ersetf rfarcotomry t hliteh ocaprhbiloexs yrelilca tive to Mg, normalized to CI chondrites. acids (n-ω-amino acids; see Figure 2) [16,17]. A sufficient numbeAr souf fficacriebnotnnaucemobuesr cohfocnadrbriotnesa coefo ueascchh ognroduripte sanodf epaecthroglrooguipc asundb-ptyeptreo lhoagvice sub-typehavenow A sufficient number of carbonaceous chondrites of each group and petrologic sub-type have now been analyzedb feoern amaninaoly azceiddsf oforra tmhei nfoollaocwidinsgfo cronthcelufsoilolnows tion bgec soanfecllyu sdioranwsnto: (b1e) csaarfbeolynadcreaowuns : (1)carbonaceous now been analyzed for amino acids for the following conclusions to be safely drawn: (1) carbonaceous chondrites of the sacmhoen gdrroiuteps aonfdth peestraomloeggicro tuyppea tnedndp ettor ohlaovgei csitmypileatre anbdutnodhaanvceess iamndil adrisatbruibnudtaionncse sanddistributions chondrites of the same group and petrologic type tend to have similar abundances and distributions of amino acids; (2o) fwaimthiinno caacribdosn;a(c2e)owusi thchinoncdarribteo ngarcoeuopuss, cihnocrnedarsietse ignr otuhpe s,deingcrereea soefs aiqnuethoeusd egree of aqueous of amino acids; (2) within carbonaceous chondrite groups, increases in the degree of aqueous alteration in the maeltteeorraittieo npainrentht ebmodeyte toernitde tpoa rreendtubceo dthyet etontdalt oabruednduacenctehse otfo taaml ianbou nadciadnsc, easnodf amino acids, and alteration in the meteorite parent body tend to reduce the total abundances of amino acids, and change the amino cahcaidn gcdheiastnthgreieb authmteio inanmo; i(an3co)i daccadirdbi sodtnrisiabtrcuiebtouioutinso ;nc;(h 3(o)3n)c dcaarrirbtbeoosnn aafrccoeeomouu ssa cqchuhoeonondudrisrtleiytse asfrlotfermor emadq uageqrououuesoplyus sallyteraeldte rgerodugprso ups contain higher abucnodnatnacicnoensht aiogifnh aehmrigaihnbeuor naadbcauidnnscd eatsnhcoaenfs a tomhf eianrmmoiaancloli yda csaidtlthsea rtnhedatnh c etarhrmebraomlnlayallcayel otaeultreser decdhc oacrnabrdobronitnaeac cegeorouousus pcchsho;o nnddrriittee ggrroouuppss; ;and and (4) thermally-a(l4t)ertehdaen rmdm e(a4tl)el yoth-raeitrletmes arhelladyv-amel teleotrewedoe rmrit aeetbseuohnraidtveaesn lhcoaewvse eo lrfo awabmeuri nnadboua anncdciaednssc oeafsn aodmf aai mnstoirnooan cagicd itdsesan andndedn acay sst trroonngg tteennddeenncyc yfor for straight-chain asmtrianiogf hoartc- iscdthrsaa iiwgnhhate-mcrheian tionh eaa cmaimdinsionw aoch igedrrsoe wuthphee irsae m othnien toahmeg ircnoaour bpgroionsu opfan irstt hhoeens cttha ferr bocoamnrb tfohanre tf hacraetsrhbteofsrtxo fymrloimct h tehcea crabroboxxyylilcica cids acids (n-ω-amino a(cnid-ωs; -asacemied iFsn i(ognu-aωrc-eiad 2ms);i n[s1eo6e a,1cFi7idg]s.u ; rseee2 F)i[g1u6r,e1 72]) .[16,17]. Figure 2. Total amino acid abundances (bars, primary axis) and percentage of five-carbon amino acids where the amino group is attached to the carbon adjacent to the carboxylic acid (α-amino acids; open circles, secondary axis) among the carbonaceous chondrite groups [15,33–38]. Because amino acids are ubiquitous in biology, the possibility of terrestrial contamination of meteorite samples is always a concern. Several lines of evidence can be pursued to ascertain whether amino acids are indigenous to the meteorite. Among aqueously altered carbonaceous chondrites (CR, CM, CI, CH and CB chondrites), amino acids have been found to be enriched in heavy stable isotopes including D, 13C, and 15N [37,39–43], whereas biology shows a strong preference for the lighter FigurFeig2u.rTeo 2t.a Tloatmal ianmoiancoi dacaidb aubnudnadnacnecses( b(baarsrs,,p prriimmaarryy aaxxiiss)) aanndd pep recrecnetnagtaeg oef foivfefi-vcaer-bcoanrb aomninaom aicnidosa cids where the amino group is attached to the carbon adjacent to the carboxylic acid (α-amino acids; open wheretheaminogroupisattachedtothecarbonadjacenttothecarboxylicacid(α-aminoacids;open Figure 2. Total amino acid caibrculensd, asenccoensd (abrayr asx, ips)r iammaornyg a txhies c) aarnbdon paecrecoeuns tcahgoen odfr iftiev ger-ocuarpbso [n15 a,3m3–in38o] .a cids circles,secondaryaxis)amongthecarbonaceouschondritegroups[15,33–38]. where the amino group is attached to the carbon adjacent to the carboxylic acid (α-amino acids; open circles, secondary axis) amBoencga uthsee caamrbinoon aacceioduss a crheo unbdirqiutei tgoruosu pins b[1io5l,3o3g–y3, 8t]h. e possibility of terrestrial contamination of Bmeectaeoursiete asmaminpolesa icsi dalswaaryes au bcoiqnuceirtno.u Ssevinerabli olilnoegs yo,f tehveidpenocses icbainl ibtye poufrtseurerde stotr aiasclecrotaninta wmhientahteiro n of Because aminom aecteidoasmri taienroes aaumcibdpisql eausrieti osinuadsli wginean ybosuioasl tocoog tnyhc,e e tmrhnee.t eSpoeorvisteseir.b aAillmiltionyn eogsf ao qtfeuerevroeiudssterlnyia calel tcecoraenndta bcmearpibnouanrtsaiucoeenod uostfo chaosncderrtitaeisn (CwRh,e ther CM, CI, CH and CB chondrites), amino acids have been found to be enriched in heavy stable isotopes meteorite samples is always a concern. Several lines of evidence can be pursued to ascertain whether including D, 13C, and 15N [37,39–43], whereas biology shows a strong preference for the lighter amino acids are indigenous to the meteorite. Among aqueously altered carbonaceous chondrites (CR, CM, CI, CH and CB chon drites), amino acids have been found to be enriched in heavy stable isotopes including D, 13C, and 15N [37,39–43], whereas biology shows a strong preference for the lighter Life2018,8,14 5of21 amino acids are indigenous to the meteorite. Among aqueously altered carbonaceous chondrites (CR,CM,CI,CHandCBchondrites),aminoacidshavebeenfoundtobeenrichedinheavystable isotopes including D, 13C, and 15N [37,39–43], whereas biology shows a strong preference for the lighterisotopes(H,12C,and14N)[44]. Compound-specificstableisotopemeasurements,therefore, areapowerfultoolforestablishinganextraterrestrialoriginformeteoriticaminoacids. Thereare somelimitationsofthistechnique,however. First,theyrequireasignificantamountofagivenamino acidforanalysis,typically>1nmolforδ13Cmeasurements,3nmolforδDand6nmolforδ15N,while aminoacidsaretypicallypresentinpart-per-million(ppm)orpart-per-billion(ppb)abundances[39]. Thismeansthatlargermassesofirreplaceablesamplesmustbeconsumed,andprecludestheanalysis ofmanylow-abundanceaminoacidsinmeteorites. Ithasalsobeenobservedthatnon-α-aminoacid isomerstendtobelessenrichedin13Cthantheirα-aminoacidcounterparts,consistentwithdifferent formationmechanismsfromdifferentprecursormolecules[39]. Thisappliesinparticulartoamino acidsinthermally-alteredmeteorites(CV,CO,CKandothernon-carbonaceouschondritemeteorites) thattendtobedepletedin13C[33,45];becausetheseaminoacidsarelessabundant(ppblevels),and evengreateramountsofsampleareneededforδDandδ15N,oftenonlyδ13Cmeasurementshavebeen madeinthermallyalteredmeteorites. Ithasfurtherbeenshownthatthermally-driven,carbon-carbon bond-formingreactionsleadtonegativeisotopicfractionation[46–48]. Stableisotopemeasurements maynotbeusefulfordistinguishingbetweenterrestrialcontaminantsandextraterrestrialaminoacids producedbythermalprocesses. Otherdistinguishingcharacteristicsofindigenousmeteoriticaminoacidsaretheirisomericand enantiomericdistributionsascomparedtoaminoaciddistributionsinbiology. Aqueouslyaltered meteoritescontainbroadsuitesofaminoacids,spanningsome92unambiguouslyidentifiedamino acids that range from two to 10 or more carbons [16,49,50]. Thus far, only 12 of the 20 protein amino acids have been found in meteorites: glycine, alanine, aspartic acid, glutamic acid, serine, threonine,proline,valine,leucine,isoleucine,phenylalanineandtyrosine. Thepowerfulseparations affordedbygaschromatographyandliquidchromatography-basedanalysesallowcontamination to be assessed on a compound-specific basis. For chiral amino acids used in proteins, such as L-alanine, an assessment of its indigeneity can be made based on whether it is present in equal abundance with D-alanine (a signature of abiotic synthesis) or if the L-enantiomer is present in significantexcessovertheD-enantiomer(asignatureofterrestrialbiology). Generally,thepresence of a diverse set of amino acids that includes many not commonly used in biology, with racemic ratiosofchiralaminoacids, isastrongindicatorthattheaminoacidsareofextraterrestrialorigin, whereasmeteoritesthathavebeencontaminatedbybiologycontainpredominantlyL-proteinogenic amino acids [34,38]. Thermally-altered meteorites tend to contain much narrower suites of amino acids, with the predominant compounds being straight-chain amino acids including glycine, β-alanine, γ-aminobutyric acid, and δ-aminovaleric acid [33,36,45]. These compounds are achiral, so chirality cannot be used as a tool for evaluating contamination. Their relative abundances, whereγ-aminobutyricacid>β-alanine>δ-aminovalericacid>glycineareinconsistentwithbiological contaminationasglycineistheonlyproteinogenicaminoacidofthefour. Noknownindustrialor otherprocesseshavebeendeterminedtobealikelysourceofcontaminants. AnalysesofAntarctic ice samples from near where these meteorites were collected, and other Antarctic meteorites that containedvirtuallynoaminoacids,providefurtherevidencethatthesecompoundsarenotwidespread contaminants. Thus,ithasbeenconcludedthattheyarelikelytobeextraterrestrialinorigin[33,35]. 3. EnantiomericExcessesinMeteoriticAminoAcids Oneofthemosttantalizingdiscoveriesfromtheanalysisofmeteoriticaminoacidsisthepresence ofenantiomericexcessesthatdonotappeartobetheresultofterrestrialcontamination,butrather resulted from extraterrestrial processes. Because the expectation is that abiotic chemistry should produceracemicmixturesofaminoacids,significantcaremustbetakentoruleoutcontamination oranalyticalinterferencesthatwouldaffectmeasurementofaminoacidratios. In1997,Engeland Life2018,8,14 6of21 Macko [51] reported an L-alanine excess ([L − D]/[L + D]) of ~33% in the Murchison meteorite, supported by nearly equal, extraterrestrial δ15N values measured for each alanine enantiomer. However,itwassubsequentlyarguedbyPizzarelloandCroninthattheδ15Nmeasurementscouldhave beenaffectedbyco-elutingcompounds[52].Separately,CroninandPizzarelloreportedL-enantiomeric excesses of up to 9% in several non-proteinogenic α-methyl-α-amino acids in the CM2 chondrite Murchison: isovaline, α-methylnorvaline, and2-amino-2,3-dimethylpentanoicacid(Figure3)[53]. Althoughisotopicmeasurementswerenotmade,theL-excesseswerearguedtobeindigenousbased on: (1) the performance of control experiments demonstrating the results were unlikely to be the resultofanalyticalartifacts; (2)therelativerarenessofthethreeaminoacidsonEarth; and(3)the observationthatproteinogenicaminoacidsinthesamesamplewerefoundtoberacemic. Pizzarello and Cronin later reported L-enantiomeric excesses of up to 9% for α-methyl-α-amino acids in the CM2chondritesMurchisonandMurray,including2-amino-2,3-dimethylpentanoicacid,isovaline andα-methylnorvaline,observedpreviously,alongwithα-methylnorleucine,andα-methylvaline (Figure3)[54]. Pizzarelloandco-workersobservedadditionalenantiomericexcessesinseveralmore α-methylaminoacidsinsubsequentanalyses[55–57]. GlavinandDworkinbuiltontheseresultsbyfocusingonthefive-carbonaminoacidisovaline[58]. Theyanalyzedtheaminoacidsuitesofseveraldifferentcarbonaceouschondritegroups: CI1(Orgueil); CM2(Murchison, LewisCliffs[LEW]90500, LonewolfNunataks[LON]94102, QueenAlexandria Range[QUE]99177);CR2(ElephantMoraine[EET]92042). Intriguingly,isovalineL-excessesofup to15%and18%werefoundinOrgueilandMurchison,respectively,withasmallerL-excess(3.3%) inLEW90500,whereasisovalinewasfoundtoberacemicwithinexperimentalerrorinLON94102 andthetwoCR2chondrites. Subsequently,Glavinandco-workersexaminedadditionalsamplesof aqueouslyaltered(type1)meteorites[15](Figure4). Takentogether,thesetwostudiesidentifieda correlationbetweentheextentofaqueousalterationameteoriteparentbodyexperiencedandthe magnitudeofisovaline L-enantiomericexcesses, suggestingthatparentbodyprocessingmightbe responsibleforcreatingoramplifyingtheinitialenantiomericexcesses. Althoughtheisovalinein thesemeteoritesappearedtobeextraterrestrialinorigin,afurtherefforttoconfirmtheextraterrestrial originofisovaline,andruleoutthepossibilityofterrestrialcontaminationwasmade. Themostlikely potentialsourceofisovalinecontaminationwasfromfungalpeptides,whichcontainisovalineand anotheraminoacidcommonlyfoundinmeteorites,α-aminoisobutryicacid[59]. Elsilaandco-workers measured the enantiomeric composition, and δ13C and δ15N isotopic ratios of isovaline and other aminoacidsinseveralfungalpeptidesandinthreecarbonaceouschondrites[60]. Theyfoundthat isovalineinthefungalpeptideswaspresentonlyastheD-enantiomer,andthattheisotopicratiosof isovalineinthefungalpeptides(−25to−16 δ13Cand+9 δ15N)weresignificantlylowerthanthe correspondingvaluesforisovalineinthemet(cid:104)eoritesamples(cid:104)(−5to+51 δ13Cand+68to+77 δ15N). Thus,contaminationfromfungalsourceswasnotaplausibleexplanat(cid:104)ionfortheobservedL-(cid:104)excesses. Additionalmeteoriteswereanalyzedforaminoacids,andadditionalL-isovalineenantiomeric excesses were observed. In CH3 and CB chondrites, these ranged from 5–20% for the former and 10–14%forthelatter[37]. TagishLake, ananomaloustype2chondritethathasnotbeenassigned to any of the existing carbonaceous chondrite groups, was found to have isovaline enantiomeric excesses ranging from 0–7%, with enantiomeric excesses appearing to correlate with increasing aqueousalterationofthesubsamplesthatwereanalyzed[61,62]. Similarly,Pizzarelloandco-workers reportedacorrelationbetweentheextentofhydrationofmeteoriticmaterialwiththemagnitudeof isovalineenantiomericexcess,suggestingwateractivityplaysaroleinamplifyingtheenantiomeric excesses[63]. TheobservationsthatisovalineL-excesseshavebeenreportedbymultiplelaboratories, using different instruments, methods and analytical techniques and taking great care to rule out likelysourcesoferrorandpotentialcontaminants,overwhelminglysupporttheconclusionsthatthe meteoriticisovalineisextraterrestrialinorigin,andthatthereexistssomeabioticmechanismforthe generationand,potentially,amplification,ofisovalineenantiomericexcesses. Itisreasonabletoexpect thatasimilaranalyticalcampaignwouldleadtothesameconclusionsabouttheothernon-protein, Life2018,8,14 7of21 α-amino-α-methylaminoacidsreportedbyCroninandPizzarello,giventheirrarenessonEarthas poLteifne 2t0ia18l,c 8o, xn taminants. 7 of 21 Life 2018, 8, x 7 of 21 FigFuigrFeuigr3ue. r3eA. 3mA. miAnimonioan coai cdaidscisdt htsha taththa hta avhvaeev bebe ebeeenne nffo ofuuonnuddnd ii nnin ee nnenaanannttiitooiommmeeerrirciicc e eexxxccceeessssseseses s >>2>2%2%% inini n mmmuulluttiilpptlilepe lmmeemetteeeootrreiiotteerssi.t. es. NuNmuNbmuebrmsebrisne ripsn a ipnra eprnaetrnhetenhsteehsseessde edsn ednoeotnetoett heth etehh ehi gihghihgeehssetts vvt aavllauuleuesse srr eerppepooorrttreeteddd [[ 3[33777,,55,5000,,5,55777,6,,66222]]]. .. FigurFeig4u.rIes o4.v Iasloivnaeliennea enntaionmtioemriecreicx ceexscseessseos fo0f 0to to2 02.05.5%%h haavvee bbeeeenn rreeppoorrtteedd [[1144,3,377,5,544,6,16,16,26]2. ]A.nAtnartcatricct ic Figure 4. Isovaline enantiomeric excesses of 0 to 20.5% have been reported [14,37,54,61,62]. Antarctic metemoreitteeoraibteb raebvbiraetvioiantisonasr earAe llAalnlaHn iHllsill(sA (ALHLH),),S cSocotttt GGlalacciieerrss ((SSCCOO)),, MMiilllelerr RRaanngge e(M(MILI)L, )P,ePceocrao ra meteorite abbreviations are Allan Hills (ALH), Scott Glaciers (SCO), Miller Range (MIL), Pecora Escarpment (PCA), Grosvenor Mountains (GRO), Patuxent Range (PAT), Lewis Cliff (LEW) and Escarpment(PCA),GrosvenorMountains(GRO),PatuxentRange(PAT),LewisCliff(LEW)andQueen Escarpment (PCA), Grosvenor Mountains (GRO), Patuxent Range (PAT), Lewis Cliff (LEW) and Queen Alexandria Range (QUE). The value for Murchison reflects the highest reported, but isovaline AlexandriaRange(QUE).ThevalueforMurchisonreflectsthehighestreported,butisovalinehasbeen Queen Alexandria Range (QUE). The value for Murchison reflects the highest reported, but isovaline has been detected in 0 to 18% enantiomeric excess in Murchison. detectedin0to18%enantiomericexcessinMurchison. has been detected in 0 to 18% enantiomeric excess in Murchison. Life2018,8,14 8of21 Therehavealsobeenreportsofenantiomericexcessesinproteinogenicaminoacids,inaddition to the above discussed Engel and Macko work. In 2008, Pizzarello and co-workers reported enantiomeric excesses of 12–14% for L-isoleucine and D-allo-isoleucine, respectively, in the CR2 chondriteGravesNunatak95229;theextraterrestrialoriginofthesecompoundswasconfirmedby δ13Cmeasurements[56]. Isoleucine(and2-amino-2,3-dimethylpentanoicacid,describedpreviously) differsfromisovalineandtheotherα-amino-α-methylacidsinthatisoleucinepossessestwochiral centers; oneontheα-carbonandthesecondonthesidechain(Figure3),meaningthattherearea totaloffourpossiblestereoisomers,includingenantiomers(R,R/S,S;R,S/S,R)anddiastereomers(e.g., R,R/R,S;S,S/S,R).Whileenantiomershaveidenticalphysicalandchemicalproperties,diastereomers donot. Pizzarelloandco-workerswentontoreportisoleucineenantiomericexcessesofupto50%for L-isoleucineandupto60%forD-allo-isoleucine,inananalysisofseveralCRchondrites[50]. However, isotopicmeasurementsestablishinganextraterrestrialoriginforthesecompoundsfromthesespecific extractionswerenotmade,andtheoriginoftheselargeenantiomericexcesseshasbeendebated[64,65]. Alsoin2012, Glavinandco-workersreportedon L-asparticacidenantiomericexcessesinthe Tagish Lake meteorite of up to 60% [62]. Stable isotope measurements of δ13C ratios for the D- and L-aspartic acid enantiomers were identical within experimental error, and showed significant enrichment in 13C (+24 to +29 ), consistent with an extraterrestrial origin for these compounds. Severalotherproteinogenicam(cid:104)inoacids, includingglutamicacid, serineandthreonine, werealso foundtobeinL-excess,butwerenotsufficientlyabundantforδ13Corotherisotopicmeasurements tobemade. Intheabsenceofcompellingevidencetothecontrary,theseotherL-aminoacidexcesses wouldbeattributedtoterrestrialcontamination. However,theproteinogenicaminoacidalaninewas foundtoberacemic,andbothalanineenantiomersandglycinehadδ13Cvaluesthatwereconsistent withanextraterrestrialorigin. Thepresenceofseveralproteinogenicaminoacidswithextraterrestrial isotopicsignaturessuggeststhattheotherL-aminoacidenantiomericexcessescouldbeindigenous tothemeteorite,thoughthishasnotbeenconfirmedduetotherelativelylargemassofsamplethat wouldberequired. 4. OriginsofMeteoriticAminoacidEnantiomericExcesses Meteoriticaminoacidenantiomericexcessespreservearecordofanextraterrestrialmechanism for generating non-racemic mixtures of amino acids. What that mechanism is, however, remains unknown. Anumberofhypotheseshavebeenadvanced. Forthisreview,wewillconsiderpossible routestoenantiomericexcessesforasparticacid,isoleucine,andisovaline,whichweconsideraproxy fortheotherα-methylα-aminoacidsreportedinenantiomericexcess. 4.1. AminoAcidsynthesisintheMeteoriteParentBodyWasLikelytobeRacemic There are several plausible synthetic routes for meteoritic α-amino acids. The most widely accepted is via the Strecker pathway, which would have occurred in the meteorite parent body (Figure5A).Evidenceforthissyntheticrouteinaqueouslyalteredmeteoritesinclude: thediscovery of suites of α-amino and their analogous α-hydroxy acids [8,66–68], as well as iminodicarboxylic acids that are known by-products of laboratory Strecker reactions [69]; and the detection of the necessary Strecker reactants including hydrogen cyanide [70], ammonia [41], and aldehydes and ketones[71,72]inmeteorites. Inregardstoasparticacidandisovaline,therelevantStreckerprecursors are3-oxopropanoicacidandbutanone,respectively,bothofwhichareachiralandthuscouldnothave inheritedanyenantiomericexcesspriortoaccretion. Asyet,therearenoknownasteroid-relevant mechanismsthatwouldleadtopreferentialsynthesisofaspecificenantiomerbytheStreckerpathway. Instead,asparticacidandisovalinemadebythisroutewerelikelytoberacemic.Isoleucine,ontheother hand,doeshaveachiralStreckerprecursor,2-methylbutanal. Wereittobeaccretedinenantiomeric excess,thenitcouldhavedirectedthepreferentialsynthesisofaspecificenantiomerofisoleucine[50]. However,thisraisesthequestionofhowasymmetrymightbeinducedin2-methylbutanal,whichis currentlyunknown. Life 2018, 8, x 9 of 21 Life2018,8,14 9of21 Figure 5. Illustration of α-amino acid synthesis routes that could have taken place in meteorite parent Figure5.Illustrationofα-aminoacidsynthesisroutesthatcouldhavetakenplaceinmeteoriteparent bodies. (a) The Strecker-cyanohydrin pathway relies on the reaction of aldehydes or ketones with bodies. (a)TheStrecker-cyanohydrinpathwayreliesonthereactionofaldehydesorketoneswith ammonia, cyanide and water to produce amino acids. (b) Reductive amination reactions involve the reaacmtiomn oonf iαa-,kceytoa nacidides awnidth wamatmerontoia panrodd au rceeduamctainnto ina cthides m. e(tbe)orRiteed puacrteinvte baomdyin toa tpiorondruecaec atimoninsoi nvolve acitdhse. reactionofα-ketoacidswithammoniaandareductantinthemeteoriteparentbodytoproduce aminoacids. Another plausible route to α-amino acids that could occur within meteorite parent bodies is reductivAen aomthineratpiolna u(Fsiibgulerer o5uBt)e. Itno thαi-sa rmeaicntoioanc, iαd-skethtoa tacciodus,l dwhoiccchu hrawveit hbeinenm foeutenodr iitne mpeatreeonrtitbeso dies is [73re],d ruecatcitv ewaimthi naamtimonon(Fiai gaunrde 5thBe).nI narteh irserdeuaccetido nto,α α-k-aemtoinaoci dasc,idwsh. iHchowhaevveerb, ereendfuocutinvde ianmmineatetioornit es[73], canrenaoctt pwroitdhuacme mα-omneitahyalnadmtihneon aacirdesr esudcuhc eads tiosoαv-aalimnein, oanadc itdhse. rHeloewvaenvte ar,srpeadrtuicc taivcieda pmreincuatrisoonr, cannot oxparlooadcuectiec αac-mid,e itsh yaclahmirainl.o Tahcei dprsescuucrhsoars foisro ivsoalleinuec,inaen, d3-tmheetrheylel-v2a-onxtoapsepnatratnicoiacc aidcipd,r eisc uchrsiroarl, aonxda,l oacetic as in the Strecker scenario for isoleucine, could lead to preferential synthesis of a given enantiomer. acid,isachiral. Theprecursorforisoleucine,3-methyl-2-oxopentanoicacid,ischiraland,asinthe However, the initial asymmetry in 3-methyl-2-oxopentanoic acid would somehow need to be Streckerscenarioforisoleucine,couldleadtopreferentialsynthesisofagivenenantiomer. However, generated for this mechanism to be viable. Another potential reaction that could occur with α-keto the initial asymmetry in 3-methyl-2-oxopentanoic acid would somehow need to be generated for acids is decarboxylative transamination, where an existing amino acid would effectively transfer its this mechanism to be viable. Another potential reaction that could occur with α-keto acids is amino group to the α-keto acid to make an imine that could then be reduced to an amino acid. In the decarboxylativetransamination,whereanexistingaminoacidwouldeffectivelytransferitsamino presence of copper ions, it was demonstrated that this could be done in an enantioselective manner, grouptotheα-ketoacidtomakeaniminethatcouldthenbereducedtoanaminoacid. Inthepresence where, beginning with nearly enantiopure L-α-methylvaline or L-α-methylleucine and the ofcopperions, itwasdemonstratedthatthiscouldbedoneinanenantioselectivemanner, where, appropriate keto acid precursor, L-enantiomeric excesses of phenylalanine (37%), valine (20%) and alabneignien (n2i3n%g)w witehren oebasrelyrveenda innt itohpeu prreoLd-uαc-tms [e7t4h]y. lUvanlfionretuonraLte-lαy-,m theitsh syclelenuarciion ereaqnudirtehs eraatphperr ohpigriha teketo enaacnitdiopmreerciucr esxocre,sLs-eesn faonrt itohme αer-imceetxhcyels asmesinoof pahciednsy alnalda nyiineled(s3 s7m%a)l,lvera lcihniera(l2 0ex%c)esasneds ianl atnhien nee(w23ly% )were forombseedr vaemdinino tahceidpsr, omdaukcitnsg[ 7t4h]i.s Umnoforer toufn aante ilmy,pthoirstasncte ndaermioornesqtruaitrieosn rfaotrh ethreh itgrahnesnfearn otifo emxiesrtiicngex cesses enfaonrtitohmeeαri-cm eextcheyssleasm thianno aa vciidabslea nmdecyhiealndissmsm foarl ilneriticahtiinragl cehxircaels asesysminmtehteryn. ewly formed amino acids, maIkt ihnags athlsios bmeoenre porofpaonsiemd pthoartt aanmtindoe macoidnss tcroautilodn befo gretnheerattreadn fsrfoemro afreoxmisattiinc gcoemnapnotuinodmse, rsiuccehx cesses as tphoalnycayvcliiacb alerommeacthica hnyisdmrofcoarrbionnitsi a(tPinAgHcsh),i rdaulrainsygm pamreentrty b.ody aqueous alteration [75]. However, this synItthheatisc arlosuotbe eiennvoplrvoeps ossigendiftihcaantta mreipnroocaecsisdinsgc oouf ltdheb ePAgeHnse rwaittehd wfraotmer,a craormboanti cdicooxmidpeo, uanndd s,such amamsponoilay,c yancldic ita rios munactilceahry wdhroecthaerbr oannsd (hPAowH sc)h,idraul rsienlgecptiavrietyn tcbooudldy baeq uexeeorutesda.l tSeirmaitliaornly[,7 F5i]s.hHero wever, Trtohpisscshy-tnytphee triecarcotiuontes iwnvitohl vamesmsoignniaifi ocra nnittrroegperno,c ecassrbinogn omfotnhoexPidAeH osr wcairtbhown adtieorx,icdaer, baonnd dwiaotxeird e, and haavme bmeeonn isah,oawnnd toit liesadu ntoc ltehaer pwrohdeutchteiorna onfd amhoinwo acchiidrsa l[7s6e,l7e7c]t. iAviltthyocuoguhl dthbise perxoecerstes da.reS giemnielraarlllyy, Fisher regarded as having occurred in the solar nebula, they could have been driven by parent body heating. Tropsch-typereactionswithammoniaornitrogen,carbonmonoxideorcarbondioxide,andwater However, no evidence for amino acid enantiomer excesses has been observed. havebeenshowntoleadtotheproductionofaminoacids[76,77]. Althoughthisprocessaregenerally regardedashavingoccurredinthesolarnebula,theycouldhavebeendrivenbyparentbodyheating. However,noevidenceforaminoacidenantiomerexcesseshasbeenobserved. Life2018,8,14 10of21 4.2. RelevantMechanismsforGeneratingAminoAcidEnantiomericExcesses Severalabioticmechanismsforgeneratingenantiomericexcesseshavebeenidentified,varying inthemagnitudeofenantiomericexcesstheycanproduce, wheretheywouldoccur, andwhether theyarebiasedtowardsaspecificenantiomer(summarizedinTable2). Onepromisingavenuefor the generation of amino acid enantiomeric excesses outside the meteorite parent body involves asymmetric synthesis or destruction of amino acids in the presence of chiral light. Flores and co-workers demonstrated that enantiomeric excesses ([L − D]/[L + D]) of up to 2.5% could be generatedbyasymmetricphotolysisofaracemicmixtureofD,L-leucinewithUV-circularlypolarized light(UV-CPL),concomitantwiththedestructionof~75%ofthestartingleucine[78]. Takanoand co-workerswereabletogenerateaminoacidprecursorsthroughprotonirradiationofgasmixtures containingcarbonmonoxide,ammoniaandwater[79]. SubsequentirradiationwithUV-CPLyielded enantiomericexcessesofupto~0.5%foralanine. Later,deMarcellusandco-workersdemonstrated thatalaninecouldbesynthesized,fromicescomposedofwater,methanolandammonia,withsmall enantioenrichmentsof>1%duringirradiationwithUV-CPL(6.64eV=187.2nm)[80]. Itwasobserved thatboththedegreeofenantioenrichmentanddirectionofchiralexcessinduced(i.e.,LorD)varied with the UV flux and helicity of polarization [80]. In subsequent work, Modica and co-workers demonstratedthesynthesisof16aminoacidsfromicecomposedofwater,methanolandammonia withUVirradiation[81]. Theydeterminedtheenantiomericcompositionoffiveofthoseaminoacids: alanine,2,3-diaminopropanoicacid,2-aminobutanoicacid,valine,andnorvaline[81]. Intriguingly, thechiralityofenantioenrichmentwasthesameforeachofthefiveaminoacids(i.e.,allhad D-or allhadL-excesses). However,itwasfoundthatthesignoftheinducedenantiomerexcessreversed whenirradiationwasperformedwithpolarizedlightofadifferentenergy(i.e.,enantiomericexcesses inducedby6.6eVlightweretheoppositeoftheenantiomericexcessesgeneratedby10.2eV[121.6nm] light). Althoughisovalinewasnotreportedasaproductintheseexperiments,otherbranchedchain aminoacidssuchasα-aminoisobutyricacid,β-aminoisobutyricacid,andvalinewereproduced. Thus, this could be a plausible mechanism for isovaline synthesis, as well. However, because isovaline wasnotamongthereportedproducts,itwasnotdeterminedwhetheritisformedinenantiomeric excessduringirradiationwithUV-CPL.IsovalinemayinteractdifferentlywithUV-CPLbecauseofthe presenceoftheα-methylgroupratherthananα-H. Table2.Summaryofabioticmechanismsforgenerationofaminoacidenantiomericexcesses. MaximumReported InfluenceExertedInsideor Mechanism ChiralPreference EnantiomericExcess OutsideMeteoriteParentBody Ultra-Violetcircularly 2.5% Dependentonchiralityoflight outside polarizedlight(UV-CPL) Parityviolatingenergy <0.01% L both differences(PVED) Destructionof14Nnucleiby 0.02% L outside stellaranti-neutrinos Irradiationwithradioactive <1% Dependentonchiralityofradiation inside decayproducts IfitisdeterminedthatenantiomericexcessesforisovalinecanbeinducedbyUV-CPL,itwillbe importanttoknowifthedirectionoftheinducedchiralityexcessisthesameasalanine,valineandthe otherthreeaminoacids. Polarimetrymeasurementsat589nm,routineanalysesfordeterminingthe opticalpurityofchiralorganiccompounds,suggestthismaybethecase,asenantiopure(>98%)samples ofthesameenantiomerofalanine,valine,norvaline,2,3-diaminopropanoicacid,and2-aminobutanoic acidallrotatelightinthesamedirection(i.e.,theL-enantiomersofeachaminoacidaredextrotoratory or[+];dataobtainedfromcommercialvendorwebsites).Auspiciously,L-isovalineisalsodextrorotatory, suggestingthatitmightexhibitthesameenantioenrichmentbehaviorastheotherfiveaminoacidsina UV-CPLexperiment. Acomplicatingfactorforuseof589nmpolarimetrydataisthatthesign,andtoa lesserextent,magnitudeofopticalrotationaresensitivetosolutionconditionssuchaspHandacidor