Engineered polyol lipid producing microorganisms

Abstract

Non-naturally occurring polyol lipid producing microorganisms are provided that have altered expression of endogenous gene(s) or that express heterologous gene(s). The microorganisms may be further engineered for functional properties of interest or may be used for enhanced production of products of interest, such as polyol esters of fatty acids (PEFAs).

Description

[0001]coer,s a,c waocn csamncs- oreoraeenee oren.. reroevresnocneans ecnareon.o. ,,e on arcuar mceroonrveannosnm rse caonesanonen aeecrea e mxoresseono o eonoenroousucenne ms acrnooorrannrsom ces,n exresseeerooousenes. uce an eroeumo anoo- caosmeou ansave a vare o uses,ncun as suracans.uracanso sersans,oam conro areen ans, e axnam wee on c aomenosun ussean a ca vnar aec a os e cmonussuers,eerens,ncun arcuura, nurona, cosmec, veerna mer acaons, acaons.owever, suc surac r,eraeuc,an,n, annusra o-accumuaon, eco-oxc, anoarnso caenr eaxao.oreerreoorrme,anceere ws a re neaeroor suesveaonam, o aernave suracans an comosonsor usen consumer en acaon annusraroucsnese oo-eses ev. rser oaaeas ac sesces ares aracve casss sransorroucnoo s, suc as ara, e a. oecnoo, wvcave acaons as suracans.eeoenn numer oeas secesaveeenaences:–,o:..oecav.... owever,omroveeer screa naurarouce an secreeoo s.nroucneerooous ane oermenaonsroucn suc s, meos oransor noeenome oe oransm are reure.eecae marers,orromucanon re mceomonsa,ne serraonos oousesroem soeecrse,s a anre c noeeone omzaon meosa are suae eens ws caneeroroucucoenrroommuuccoossee o as a saoe c aacrosn. , a snource.oeors souscn ase mss ver arao.mrovneer o canereoree accomse ncrea anno an eecae osnecawa,ncreasnenraceuarosne exresson oncreasnenraceuaroos ooos.urermo os oa acs, anor osnecawas caneoce aneerare,oncreaseeer o , comen mrovne caac oe rouconaoanwaaw maas omrs caneoce. arroauoce,o arm saraonn. oe ac-o,rouconroxaawoan os acre-coe,o eeo serove ormnae oone or o manno an aceaon o-a ac anoo, secreon.ara, e a., e cormreaon, acoesnaoencawanvovese ses oroxaon o ac-o, eseronormaon, re , an secreon.uave aceranserase enzmesaveeenene revousrosearcersneenome o.awanenss ase onomooo aceranserasesormeaorrmmaareona oome ecosae.roucaono. mar, canaeenesoamocnosness wcnncueewseeeneoneo an-ra acs maeocae anaoromoccuos.nuoes, en ae.s,s. oeuaero exnzamoen r oesoonm ons- anure e so oroars e-cuamnu roxaua a an ocs nss nsononwown aaroxaon oon cana acss caaz n, sao mas wereasearo e eenem rom .ecman xaon o sor canss caaze m roucomn.roovmne reveewesne,r e aa a veu.,xeeoneu nosvoeaes accr snn meess mamroveeer o moecueserveroma acs.eean, e a., .eovesra o smureovneers ooruoesave asoemonsraemrovenraceuara ac accumusnooorua oa,mrovnuxoa acosness oennvovese ovaeroenx.resan, e a., o caroxase, wcmrovese avaa o maon-o,e susraeoraso an o ace- osness.noer eecve srae manv c eroxsome oveocneeraaon o sneacor, resm aonvnorae moconra,or exameeen aeroxsomaoeness orae, e a., -aeca cooecn mzome oxases, oreenc-oeroenases. eroucon o ace-oor oesnn seusessaranseoasesa anmoran roenranseoases ma enaeerer.eenas en aooorua.us, overexressnracceross aresrouce eassa asoro.,uceareuanes onraceuar nce s an ,s woc are common sorae moecuesor euaroes.ara, e a.,ncrease er woueorawocromoe novoa acosness, a sraorwar wao ace-o moecues, wc couensennceoss o s oroncreasee reccn o so eosness o snun ens wroreaeransneor o an. ac. m.oeaenromo.,, ono aaccero moecue aaccero acranserase .noo aoruoa carrer rooreuooes,ermar enzme resonseorss cuz, e a., , w an uncear enrsae,, wc.snvoven ormaonnarrowaoca, anoer oeanouseas meaosm oer aconvreourse,acceroasesreaown moecues, aownmrovese accumuaon os.e maooecc moenncaesanocn oueseases mamrove rouconn sransuaes an, e a., .verexressnese enzmes wereas aarannoossreorvueceromroruucoseeen onoeso se o acwc ooum s rouua aee esanuwns. a.nooammoonc,n e ao.s,nes,sa serucurroaen raeaeco,eeon o enzmes encon a manno-osae rouconse, mannoeroenase, an an araoeroenase aoseamocn er.ueer,. e a., verexresson o enzmes enconese acves cou resun ranc s a crca co-acorora acroucon.nooorua seces,e oxave . o seseemnaosceosaeawaas ae roen eneraonnero e a. aanceeween creaa aerne exresson oeenoseosaeawa,eroer e aceve. ne susrae avaa o arao an oerosnecrocesses ma caron moecsaveeen reoreoe consume aerroucon.man, e a., omex arsoeaues suc as s are oenerae ouse oe ceo enaeer consuen arr en u more ecen.ecreeases arenowno enae oeanouseasse ao aw roaenoecaraoaones o exrace.ueamrovns.eseev meoneecauu,e es m aa.,mrovemear mero oecues m.a meos aonn-naournauc occurrn mcrooransmsarouceoo s arerove, as we as mcrooran eoe consrucsor mane mcrooransms an meosor usne n osnmes asoecro, auc neon-onaouras ocncu mrcroa cuure. e non-naura occurrn mcroor rnoo roucn mcrooransmsrove. aere exresson o ansmncues: aeas onenoce ou enoenousene mcroora aeas one enoenousenen comarsono a naura occurrn aaren mncsrmoorroamn wsmcrome w nocn-naeur naon-n oaccuurrarn o mcccurroronra mncsrmoorsaerve orn comarsono aeas one exres nsmserve anor oon s soemeec eemse roommeee enroso,o roueus n coono n-snsanuuc nraeo o: oe acc.urrn mcrooransmrouces one or more aomsn -roxa ac moeromo caron esereeon a su esaerreo a suar acoo moe an aceae-roxa ac moe rous esereo acoo moe a suar acoo moe comrsn non-esere rox comrsn a mannoe o cra arrox en o a-roxa ac moe a suar acoo moe moe an aoo eser oa aoaa accone ese.reoe carox en o a-roxa ac n some emomens,eer o aeasn on oeneo emoomena,seroouo s a . naura occurrn mcrooransm, e.., wenrownn au meum ce e non-oe naura occurrn mcrooransmrom wce ,sncreasen comarson erve orn comarsono aaren non-naura occurrn mcrooransms mcrooransmserve. mcrooransmrom wce non-naura occurrn mcroornan sosmmes emromomee snus,ne noomn-naaurraa. occurrn mcrooransms aeas, suc as a scomco e mcrooransm maeromeum some emoa omreasomcoa.e mcrooransm maerome orerorooaes.n ooorua,onso,e mcrooransmsrom aenus seeceromerou conssn o: meo, a secess seoroous, anorooomces.e mcrooransm mae,us no oovaa,oooruaecraeoromerou conssn o:oooruaaavae,ooorua a.auena,oooruacvovae,oooruaramns,oooruaauena,ooorua arenenss,oosoroo susa rerocara,oosoroous a. coosr,ooorua anoosoroous a. unenae,oooruaawanenss,ooorua mucuanosa, seeceromerou cons nsann o.e mcrooransm mae,us nomeo, a sran aevae sran - ,o:oooruoaorauaevaae sevraaen sran -- ,ooorua aevae sran -,oooruaa .,ooorua aevae sran - evae sran -,ooorua raocvovae sran -,,oooorouoaruaooavuaa senraan s - ,ooorua auena sran -.,ooo ran - ,ooorua a.auen ruaauena sran -,ooorua oooruaaa sreranennss sran- ,-ooo,ruao sosaerocara sran - , ,oosoroous a. coosr - ,orooosoours ao.o couoss ar. s nraann s- - ,oosoroous runenae - ,oo ran , an ooorua m oruaawanenss sran comarsnon soomee em exoremsseonnsu,c eveea en oxorsea es s esnorann oeevne- ou o- s anen een. noeen noausuraene ocs aeren mcrooransmrom wce non-naura occurrn mcrooransmservecurrn aaren mcrooransmrom wce non-naura occurrn mc orn comarsono or exame, aromoerore enoenousene maer roeoraacnesmserve. reocmreoasern, a,n oro cr aan’ unnraens reaeua reono on exres asnono or ae’ eno menaouse a w enee an, a oerreeren e rncreasn, oe sa o m asranscrerome e euaon rom noenousene.n one emomen,e nuceoer oe enoenousenes reace omooous recomnaon, , znc-ner u noasem, or .n anoer emomen,e enoenousenesuseo aee, suc as, ec vruseeroo,e auxn-nuceeron , an-ermnauson o uun, oreoacco oe en nae,n oreroncrease,ecrease, or canee reuaon o exresson exressono n aene vonou e.esrn ee oxn nae em. eme,oem eenno,eeno eunsoeneeno muaseenensocneoc oeu, o sue onrce, or reucen omooous recomnaon, , znc-ner nucease, or .n ano eer eemomen,e e rnoozmeneousenes sence nererence, sencn, ansense oonuceoes, ns, c oerr aan emo-maesnes, mee noon,- snuacur as,u nomeo as an as. enoenousnoce ouene, senceene,a or occurrn mcrooransm conans an enea encoes an enzmen aosneca rewuaconn exressoneve o an enoenous werene mcro orroucon orac cero , , oransmrouces aeas aou , , , , , , , , comarso,no,e nau,ra, occurr,n m,croor,ansm,rom, wc, , , or ess n mcrooransmserve orn comarsono aaren mcroor e non-naura occurrn occurrn mcrooransmserve.or exame,e enzmeansmrom wc e non-naura roucon o mae an acranserase enzme, suc as,nue noosmneeoc,aawaor acranser c cero nocen ou oasee er. n eem, soencmeense,ne,e o nro rne-nuaceura ex orcecsusrornne mvecr oooransm conans an enoenous an enzmen aosnecawaorroucon o a caroeno an. enooenousenea encoes eosnecawaor caroeno roucon mae aunconar excaomenee, cec enzmen snase ase oene nocen. ouureenre e,m seoncemenesn,e, oer n roen-uncaeuran ex ocrceusrsronn mevcero oor anan esm conans an enoenous encoes an orone-osaeecaroxase enzme, a cosneenamoneansousenea a sexcraeseeo emnzoo asmee, e, a n a- zmereo,xro asx nomac ena- oraonosoerrraoro e, au omoo, o aesne e,n aaseereonxoso-moaar aacas-eo enz smne,a asne a ecnz-moe, a cero enzme, aosaae roase enzme, a enzme-, a-eorsna-eeeroroenase enzme, aoso :ac cero acranserase en ureraresor reeunc, onr a senroraunsmemraneroen.ne sene ar ma ose reorenorae, e a., .ncenoens raese onunconaenomc sues, suc as accumuaonn oooruaoruoes areooaresoroer reuconrae, e a.o reuce roucn accumuaonn ene wn aueras ereesr. e emxroessmoennesv,ee naon e-nncaoueras a o mcacnunrrno mecrorooransm conans an enoenous osaeosaase enzme, a manno--osaee roeennaassee enzme, a manno-- enzme, an araoe roenase enzme, aucose--osaee enzme, a D-xuonase osouconoaconase enzme, a-osouconaee roenase eroenase enzme, a- osoucosesomerase enzme, aransaoase enzme, aranseoasenz eme, a ceroase enzme, a snase enzme, an ace-ranserase enzmnez,me, arac- ac aa roxase enzme, a ransorroen, aa ac snase en azomne,-c ana ana- o caroxase enzme, an craease enzme, or a maaee roenase enzme.cene- seneomnc sue aers ma en ureraresorncreasn rouconase onunconaoncrease , a scucucm asose reorenorae, e a.nenes reore orae, e a. ro uaonn ooorua areooaresorncreasn accumuaonn n suocmneeass. eerooouso enmomens,e non-naura occurrn mcrooransm exresses a e seecae maruceoea encoes aroenaroves a seecae marer.or exame, or an enzme er mae an enzmearoves anoc ressance, auorescenroen, eeroono suosmea o enmro ucou eomcees en as, re a eeu n nre coon- m ensae auarraoc ac o-crcoucrurc en. ro mcarsoeo,r aansm exresses aranserase, aon-cana-ac aa roxase, a ransorro senn,ase, an ace- snase, an ace-o caroxase en aa ac e r zme, an craease enzme, a manno an oenase enzme, a manno--osaeosaase enzme, a D-xuonase enzme, o asraoouceonoroenase enzme, aucose--osaee roenase enzme, a- osoucoseascomonearsaes enzme, a-osouconaee roenase enzme, a e roenase e enzme, aransaoase enzme, aranseoase enzme, or a maaewo or monr aen no e onen -nrz a asm uraeec., o acc murcrrona m ccuroourreanssmrovse as, wesccrencuerees:n on ae cu oru ar consorum oeas aoroau oo asrouce e mc e meum an a mcro rooransm.n some emomens,e nn asnmoser s aescreece,eonoucoeoen coonseru ccuure meum. enoenousene ornroucn aeerooouses areroveor aern exresson o an mcrooransm.n one exame,eonuceoen ceonns aruconocuesroucnos seuenceasomooouso aeas aoron o aareeene se: aueromoer a nuceoe mcrooransm a nuceoe con seuencea encoes aroenanroceneenome oe marer an aermnaor, wereneromoer anermnaor seuence ves a seecae ene exresson oe con seuencene mcrooransm.n anoesr are caae orvn onuceoe consrucncues: aromoer a nuceoe con seuenc eexaomr ae,e ene an a nuceoe con seuencea encoes aroenaroves a seeecearooous wereneromoers caae orvnene exresson oe con seuencesnee marer, mcroora eos mnn scosm rom. oer eamnsom,moern esx,amee n,ucne aoccoer caoncne w seueen ccoeson co usoane oemsczreeor exressonn ae.n some emomens, aeas ao nae or seuence a u oe coonsne nuceoe con suc ree mos common coon or secon mos common coonneos mcrooransm, ae as.,or exame,e mos common or secon mos common coonescrenae or mcroorna some emomens,eromoersnucene non-naura occurrn nn ssm. ressance, aomueo eremscomens,e seecae marers an enzmearoves anoc n some emoenmerones,n, oer n aunc enzmearouces a reure meaocrouc. encoes an amno ac seuenceaaecoaee con seuenceor aeerooouseneurer eeerooousene.or exame,e amnos aeecon or recover oe exresserouc o mancue as-a, e.., a seuence o aeasc s seuenceaacaeseecon or recover resues, a -a seuence w e amno acx s,e suucenc as sxo nne consecuvesne ca seuence w e amno ac seuen e :, or a n anoer asec,onuceoe conscreuc :. anor a an unransae reon anor an exrs reaceeromoer o an enoenousene,n one exame,eonuceoe consrucncessea, e..,oacaeeecon or recover. aeas aoron o aareeene seuencenuees:e a nuceoe seuenceasomooouso seuence, a’ , anor aonuceoe seuencenoame e oe mcrooransm an aromoer exame,eonuceoe consrucncues: a nuceoe sncoes an-ermnaa.n anoereas aoron o aareeene seuenceneenome oeeu menccreooraasomooouso a seuence, aermnaor seuence, a’ , anor aonuceoe seuennsm an aromoerermna cea encoes a- aseenna r a. annosoerrm aese wc, a an rec oomenaonnouco roucn mcrooransmsrove, wc n anoer a eoe consrucsescreeren. roucn mcroorasnsemc, w a mce cosroveorroucn a non-naura occurrnoo occurrn mcrooransmro onans aeas onenoce ouenen comarsono a naura comarsono aaren mcrmoo wc e non-naura occurrn mcrooransmserve orn erve.e meoncuesrraannssmrom wc e non-naura occurrn mcrooransms onuceoe consruc asescreormenren a, woconcuroucnos mcrooransm w a asomooouso aeas aoron o aareeenee sse: aueromoer a nuceoe seuence mcrooransm a nuceoe con seuencea encoes aronceennaeroevnomese oe marer an aermnaor, wereneromoer anermnaor seuences are c a seecae ene exresson oe con seuencene mcrooransm, werene nucaeoaee s oervn asomooouso aeas aoron oear uence mcroora eeene seuenceneenome oe enesnancsmvaesru orseene seuence omooous recomnaon, werenesrue roucnn m ancorooerr aasnsee mce, w ae mn ce cooe m nascr nsrooo avra eens asom or. nero exurcensse a noen-enraoouraous ococurnrunceooo comarsono a naura occurrn mcrooransmrom wc e non-naura occurrnen mcrooransmserve orn comarsono aaren mcrooransmrom wc e non-naura o mcccurorronra mnscmroo wran asmosnucerevoe.e cones mrueco wnccunceusreasn:s aorrmomno aero a nouc roucnos seuenceor aeerooousene an a nuceoe con seuencea e eoe con roves a seecae marer, wereneromoers caae or ncoes aroena con seuencesne mcrooransm, weren sa nu vnene exresson oe eerooousenes exressene mcrooransmceoe con seuenceore n an oor ae cro anssoercu,m a m oewoo oro mrorroe nuocnn-na a. rown one uroao occurrsnr movcroeor.anesm mse aoncues erenn an envronmen, suc as aoreacor,a conans a cu sescre an w nurensa are suaeorrow oe mcroor ure meum, uner conons roucs, weren aoo roucsrouce e macnrosms anroucon oosnec cuure meum.n some emomens,e meose oransms ans secreenoe connuous rormen aac,eac, or e cuuren m soro emcees um esm. .no sommeen es,meo mmeeourerncues recovern eoo roucrom wouss oe mcrooransms orns,eoo s recovererome cuure meum maeenseran waer, a exracon w an oranc soven.or exame,eoo cuure meum a mecancan recover oeoo manvove searaonrome sen. meo suc as cenruaon, connuousecann, orassve meum.nn so smomee em emoommenes, aeas aou oeoo s secreenoe cuure m.n some emomensn,s,eeoooo roausc asenncs o aou. mo aou. n anoer asec, aoo asroucen au neon o-nnea ourra mor oeccu. n a meo asescreeren,srove.n some emomen rrn mcrooransm, erou conssn o: a- roxa ac moeromo ca,reono aoom s seeceromo a suar acoo moe an aceae- roxa ac moe esereosnee snu esere moe a suar acoo moe comrsn non-esere roxrous eser ar acoo en o a- roxa ac moe a suar acoo moe comrsn a manneo oore carox accone es.enr seomeo eme coarmoexns e,ne o arao a aoo- roxs aa ac. moe an aoo eser o aa ae onureeren s coonwcsenraooonosru oa noaurevaeransorme w a nourseorcn seecon cassee, e ures – sow aesn ssceoemracn. s cor reacn a semen oeenome w a anecna ae s meaercear.e m:arear.sm: coonmaononous reco wm sneauoennceesweoemnonoeaoruso araenmoemncs reon rouec seeercomon ceasasm aneenome oe oransm.:eenomc seuence reace sownnuuress asm –ee. s ar se aosws mnoeuaarr asseems w o coanssmervesonocsa o-ueneenraes.:cemac omnnearasmsn aoenae reaconeneraesareasme overans.: e assem o aeasm s scemac sows ures – sow us meouoranocn ou . exresson.:c r assem o exresson consrucsoreerooousene ocus conanenma anc s. cowse assem o aeasmesneoneraenoe aroou.eacemen ooe exresson casseeane ouwaracna sesan reenurn conn o e roou seuence reners. co coones we raeran consr xresson consrucs.:cemac o mouar assem o exresson assnuecs usn overaanoseenneraaee assema.romoers, con seuences, anermnaors are ar nna ses.omnnesearasms weocuso croaneananc aoneese assem o aeasmesneoneraenoe ooorua n exresson consrucor exresson oe con seuence n u. : rereserensa – sowoooruaaevae sransn wc aseennoce ou.ransorme w av see ma or vewromeransormaon ooooruaaevae- aarae sruc ou wrer nourseorcn casseearene enes sown.:n coonuer r s sowneeo we coonesuer anowere anoom r an one reor rmerso cecoreussrruaee coon coorenoe.:aram onn ses rmers,emonsran remova o on oeomooocous.:e sown usneseromeenure e arencueereor c us recomnaon.oeeseanes are ure sows reresenavees o ar. m veworransme anuorescence cocnrsorsucco emmaes o.aevae- w eer a seecae marer or w a exresson ureosn-eo.wawanensnos romoernerae ae ocus. nocou consrucs aneocaon ocromun.aevae-. sows aaram oe e resus o usnenernar ers useo screenorsruon oeene. sows . mers,emonsran remova oe w-e seuence on a.aeuvrease-- s sroawn w r aeuscruone an anncerenaesenee o erramucose o vew o mcroras o- ces w w-e orsruea. seowns reresenavees nroenme mea. sowsee o erramucoseromeesr aerermenaonn ass. menaonn sae ene w au nreewsrom –oer s, wow a or wesonu sc aem-earmcnoar reeacenae orroemroone.r o an enoenous ene w au nreewserm –naor, s wow o ar wesoun s ace-meramcnaor reeacen oreeroenrmana.or o an enoenous aveeenon e-nnanuereare occurrnoo roucn mcrooransms areroveeren, wc enoen o exresseerooous seecae marers,or aere exresson oner anouosreenes o,ncouonnsocroouu ocer senn mcncro oa en cuoueren.ousranesnoersm, aanonor meormosro avemen onuceoe consrucsorroucn suc mcrooransm srans areescr n cuurn enneere mcrooransms asescreeren, anroucn e.eos o e mcrooransms oo sn cuures o nessen aere o aseorwesscre. same meann as com eeren, aecnca an scencerms useerenavee eons.neon, e am.o,n unersoo one o ornar s ne aro wc snvenon anons,ewor ,c anonara oe crooo an oecuaroo, secon e.,on e erenna, rove one o s war aamen,ereareronsconar ooo,arernvenon.n meos an maeras smar or e aconar o man oeerms usens eracce oresn oeresennven uvaenooseescreeren cane usenecnuese or macoecceu oareooresenncnuvennoo renn c w. om emnanoe,c unnesuse os,e mrwcsroenooca,e c, convenona ocaeumre,sor, wc are wne s oe eoo, an er ar.ucecnues are exaneune orn euxcaemoee,oneceusasro.nn.:a, ea.o,raoruarnrua, secon eonamroo e a., .usue e enroocosnoecuaroo . eneranser a a.n, esx.,r :eomerase aneaconus e a., es., an umerc ranesesrsovon:eeareonra aorerncaunsuvareer, . ness oerwsencae, nucec acs aree w orxee on numersenn e rane. ac seuences are wreneo r n amnoo caro reenaoo rn, rense'cove' o.renaon amno eno “ns,e” “aenrm” a “nao “ue””sn ucsueeerueran roe merences unesse conex cear caes oerwse. exame, “aou ” reerso an nu eanus or mnusenercen o a vaue.or rou ane “acer caaeron-romroxe aam c a ecer n” o reeweereseno aa an ac. comoun werene rox s useeren,eerm “ a acs aceae . roenaroves a sm anaoous seuence” reerso aoe e seuence wn a a reerenceroen.or exaamruen,cno en,eorear re soruncsurea, a connaorn c aonns aervea reesx oure as wea r seseeeco s ereumceunre.,n re soamceem emeno ammneon asc, ansaono auns a sneaoueonucses se areuenrocev meanaan reseu sanme srucura ex n a smar ormroveuncon w resecoearenroenrom w ac varan enzme erve. e varans unersooeo mraesaen “ “aeneorr, o”r aso use” oeree enenmenes s seoc cocnaoonne a,n.e.n, eeem ceanmss,a so au e conuncve resenn some cases an suncve resenn oer cases. er eree o reaoena or uenreraeseeno oeorse eanemeen ese smeencsc saececnaee unneess ceare “anncaore” caousmee,e c wns one ma raerr. enues, aasn a nuoan-em sucn a esx “acmomer,s an re”e craenceo “ anor,” wen usen conuncon w oen-n n reer,n one emomen,o wou oona ecemuenns e oemerenasn oernaen n anoer emomen,o wou oonancun eemens anoer emomen,oo an oonancun oer ces arere ec owe. nrm an " moraeancaor" or “ermener” reerso a cose orara cose vessen wcn some emomens, rane.e ces mae,u are no necessar enu susenson. rown anor mananeenr coannace wnenu susenson, ces ma aernave e nomeo a so ro , on, or wn anoer non-u susraencunu “on w suor maera. seuence o amn seuence” or “ ” reerso aonuceoe seuencea encoese suae coeneromns “ocu ac orurs ron o w” a re,neor aseouroew.n aouaon o ces, e.., mcroa ces, uner eerm “erverom” enco or so meum. “oanaerom,” “soaerom, masseseerms “ornaerom,” “oanerom,” maeranss ornn anoer” s an “creaerom,” anenerancaesa one sece reerenceo anoer sece maereace maera oraseauresa caneescre w roucesa usseeeren,eerm “exre.sson” reersoerocess wc aoe es anransaon one nucec ac seuence o aene.erocessncuesoranscron s ceauaeneces o ee u.se. e.c,neenree ex sne, “e reux sesnr oce nesson oa ve esc co oore” nra reers seuno ene a ceon o an ceo o on srs . mruoc urce c so cun onaan roen s ceo anureonc see co sunen cnces romoero aecranscron, an oona oeraor seuenceo conro sucra ue a seuence encon suae m rosomenn ses, an seuences wcn csocnron, a aermoneanoan oenoramnsccrnseorn. anncerarnasnsaoormn.een voe ac sour maaeeo as,asem vec, aor maae rearr cacoee, a or smunconneenen oeosenome, or ma,n somensances,neraenoeennome nseen.eeoanscmues suce m ooser coormmmso on ex usreessoornm v oec eoxrsresaso sner vveec eoru.vaoweenveur,nceonnsv aenons wc are, or reonsreceneec n”o rem n “e aneer,sn ooo o awnn wn se ee a cmr. oenn reaosnsnv aosv ween asrnoeurvcennn a soeuee e anncues eweennvua con semen ncesnrons “enenocou” or “nocsouex”o rns. enome en, e..,e use oenec eneenrsooss o an enoenouseneunconrou ene seuencesromeos mcroo eernonacvae or remove one or more seccserve ransmrom wc e non-naura occurrn mcrooransm reuao “. n oen eex sreencn” or “enenocown” reersoe reuaon oene exresson, e..,ranscrona sson o an enoenousene,n a ceorevene exresson o aene ae reerso aeoer o nmr uc “ra eens oearoo eona orourse o”ve e onr. “exaoeoneosu nso,” w nau rreaere onccceuron a a soencuceeoe orroen, snene aeerm encomassroensa are encoe naura oc cce, e.., aos ce. muaeenes, anor snecenes.n conras,eerm “omooous” or urrnenes, reerenceo aonuceoe orroen, reerso aonuceoe orroe “enoenous” w e ce. na occurs nauranuncon asn usoer sruecreunre, “ asom ao reoeroeunsceroreone”n o.r “oommoooos” m reaerseor aroenaas smar unreae seces.n some emomens, aomooas auaernom evouonar reae or srucure smaroa o a reerenceroen,ere oena aaorw,nerar anorrmar semen orramenne reerenceroen w an anaoous semen oor reacemen o a omoo, w reuce sruveness o srucure anoruncon oe rererramenrome comarson w reacemen oe semen orramen w a seuenceroemnc ae nroenn roen. on-omooous carace “rzoemoo roeusesc reocno,m srannaonnv”a resoenrs,oe s ouncoemsse oo r aear mee reaseoccer eoncess,s crossn over. srocess can resun a newonuceoe conannenec moc aan wc nuceoe seuences o aos oransm are aere w an exoenousonuceooenn saeruence usn seuencesne exoenousonuceoea areomooousoe reon e seeor aeraon. e exoenousonuceoe seuence encoes aenerouca can r mar or comee unreaeoe reace enoenous nuceoe seuence.omooous eencoomennoaon cane useo remove,n , aer or mo e exressoneves o an onuceouseo, onuceoe, exress a smar or reaeenerouc o an enoenous enoenousener. exress aeneroucasssmar or unreaeoeenerouc o an ce s useeren,eerm “os ce” or “aren ce,” usenercanea eren, reerso arans ore cceeneno wc a recomnan exresson vecororroucon o aoe e mae eroeno mra ex nroes nseocnes oeoe e.os cesncueroen o a sneos ce, an comemenoe ornasaarrene ce comueeoe nauerncan moroo ornoaenomc mae naura occurrn or non-naura occ a, accena, oreerae muaon. os ceransormen vvo w an exresson vecor.urrn. os cencues cesransece or a concenreerm " ro c caron source” reerso an oranc comoun as souen waer waer oraea s aeorn sms o "rea ureor n woan acer ca or. eosn source" reerso an oranc comoun asnsouen e como “un-sroxroax ac” reersso aana ac. werener caronrome ac en oncues “reanesrmec “onnr,o” “urca aee ns,”. ornmaeo cno,”n oerx “r onsern a nucec ac seuenceno a ce, ac seuenceno a euaroc orro ansucon” an reersoencororaon o a nucecncororaenoeenome oe ceare.o.c, c cer werene nucec ac seuence mae convereno an auonomous recon, orra omosome,asm,as, or moconra , or a mcroo “nraaunrasm a osccouurrnn” or “w e” mnsceronor eaxnsrmes rseee.rso an unmoe mcrooransm more mua “noonns-n oaruraaa osccuern ernn na”u e mrec.rooransm reerso a mcrooransma conans one or mcrooransmr neca moen comarsono a naura occurrn eermom wc serve. a aowsemo “oeerrao ne” reerso auxaoson or arranemen o sece eemens neo a con seuenrmcen concerorn aou an eec.or exame, aromoers oera s useeren,eerm co “noronsuceeoranes”c rreerosn oe con seuence. en an an ree-mensona srucure an sne- oro m auomercorm o nuceoes o an oue-srane,re-eca, ec., wc conaneoxronu-sranee.., sne-srane, anaos or moeorms oeoxronuceoes or ronuceoceoes, ronuceoes, anor orases orer anaos.ecauseeenec coeseeneraees,ncun moe nuceoes useo encoe aarcuar amno ac, an eresennvenon e, morean one coon mae wc encoe aarcuar amno ac seuence.n e o moenco nmucaessesonuceoes anao mae use, soon aseonuceoe reanseesreuncoonae or u nnuceeroe o use,ncun mocaonsancrease nucease ressancee..,eox,'- conons exaomseo,ro raooaacesv,e e ocr. n.onaraeso macave asaoees onrco arncoroarse, e.or.,uorons.es oeeermecoo-nn oe ur, c caure,orncuese e nucec acs .onuceoes mae naura occurrn or none-onauera aso o ancc neu arocrrnasn. eeraee eo..rmos “ senuuo ecnen couce e oeos nu me ca,” “ eo cnounc esae mnc ac, ae,” an nerru, “o oro eonuc, n ae ono n-noe ur” c m a eore u oese e coomremre osn n anor or moreosoesernaes mae reace aernavennrous.ese aeens.ne nnrousncue,u are nomeo rnave“o , emomens werenosaes reace wca eea”c, or“'snoaeee”n,en2“amae”, , ', or2“ormacea”,n conann an eer----nae, ar o,r a suens,u cec or unsusue a - oonan aonuceoe neeeenca.onuceoeosa ma, cecoaen or ara.o anaes comnao near or crcuar or conan a en oernear an crcuarorons. xemaromos “oo” reerso an oranc moe a conans aeaswo rox rous. caron, xo-ncue cero-caron, erro -caron,reo -caron, arao- caron,u caron, ro-caron, manno-caron, soro-caron,aaco- caron, cccoo, a-cnar vaone,no.on so-cmaer eomn,onomseons,- acarooon as r cecrecs seunear aco aoen,e vroaemormoua- 2 aceae “o-op - es2 reorx o w a aearen ac acs es”e o- rr. “e ro”u reerso an am c moecue comose o an ca D-m e carox eno a or caronoo, “oannoo or” D re-aerarsoo a, w com vaorunnerees o aceaons. ac. weren aoo moes covaen aaceo aa reconzes u asse areoreenn, “oosee oe s” renerseo a ar c.omeo csonon comrse o amno acs anor amno ac resuess useeren.ee venona one-eer orree-eer coenercanea ereno reeroomers or ammsn “ooe e” an “roen” are use orrance, ma conan moe amno acs, an ac ms o anen.eomer maenear eerms aso encomass an amno ac omeraaaenerrue non-amno acs.nervenonor exame,sueonormaon, cossaeoenn, moae naura or osoraon, or an oer manuaon or mocaon, suc as conoun, aceaon, comonen.soncue wneenon are,or exame,oe easo cnon wan aaen more anaos o an amno ac ncun,or exame, unnaura amno ac n one or mocaonsnow s, ec., as we as oer exraceuaere,r wm “n cron suce on ar nc”. unceuees seocreoen oroucon o comounsnraceuar an voume “erro unucvme”n re ae mrscrooae aemrmouenna oo an su c rosom ceasnsco .eun oros r euro xcaeme a ce m.crooransmer un e exresse asrams ooo rouceerer o souonmeer,oour.o roucv ma naeran “romoer” reerso a reuaor seuenceasnvovennn omeraseo n “n scron o aene.romoer mae annuceromoer or a consuveromoer. reuaourc ceromoer”s aromoeras acve uner envronmena oreveomena encoe, aneon veermo co “n rrsesc. aonm cenasn c,”on reaenrsno suecneco mnaucereao.ees., nuacecas aceesn, meooeeoese seuence or exresson caracerscs, suc as muane con seuence aers aereoee,usne con seuenceoa o anoerene,acn aoenero unucee an conro o aerenromoer, exressn aenen aeerooous oransm, exres re aecrease or eevaeeves, exressn aene conona or consuv sn aene aroms naura exressonroe, anee.enera recomnan nen mannereren an cesaseereon,aveeen manuae man sucaeu acree nco acs,oees, nucec acs,oees, an c encao reae eerms “recovere esounn naure. maerae.., aro ,” “soae,” “ure,” an “searae” as useeren reero a wcs naura aesn,, nucec ac, or ceas removerom aeas one comonen w we, or aesaoscae,or w exeam,e, a a concenraon o aeas we, or aeas samen wcs conane.or exam ae,eaesseerms m wae re,e or aeas. we oe susana or essenareerom comonens wc norma acrcoom a maaera wcs sae, suc as,or ex n asounns nave eerm “seaeme, annacooca ssem. aos c cve marer” or “seecae marer” reerso aene caae o exressonn vecea aowsor ease o seecon ooseoss conann annrouce nucec ac or suor.xames o seecae marersncueu are nomeo ressanceo anmcroa esancese..,romcn,eomcn, or coramenco,enesa encoe aroenas aveacnaae wen exresse, orenesa coner a meaoc avanae, suc as a nurona arcua “e r su, osnaneaosr ceee”. means no morean aou ,,,.,., or. o a nucec aceus s orraansc oees “n es au csom easnoaso ca snm. maera”n asn “asu asoannauceoene,cao”nee ceo,nex o aeaswo o aoeea conans a s or reon oroman , , , , euenceaas aeas aou , , , , , , , , or even. s,euen,cee,n,,n com,ars,on w, a re,eren,cee., , , , onuceoe,oee, or reon oro ., w-e oee ma man o aoee. reon oroman o a oee seu ceonncea.n,eor exame, aeas aou,,, or amno acs wn aoner , , an uenc uesnen san maaraerameeeremne usnnownrorams suc as o.:- eno, e a. roc.a.cars..c.ee,: e..,saur,n e, e a a.. .rooc.. anaa.secsas.uc.c: avaa anerouns, ee a. ene: .owareorerormn aaases mae searce usn aeoanrasone,neroroecnoo normaon.so, .n some emomens, susana enca eo a.e esroecr. ona.c oane. oc.: - conservave amno ac susuons.n some emomens, susana encaro more aremmunooca cross-reacve.n some emomens, susana enca nu e es moecues rzeo eac oer uner srnen cononse.., wn a rane o mceecu ac srnenc mo aaceo “s. euacar a cacrooon” a reomer.soxe amn oraran scu comoun conann one rox rou– c ar acoosncue erro -caron,reo - caarroonn,, arao-caron, xo-caron, ro-caron, manno-caron, soro- “aearc” reoers-coar amoonu,n an o au scuosan-ccaeron. mcroaermenaonrocess.or exa rouce a mcrooransmer un voumen a ro me,oo er mae exresse asrams ooo “urcaenseecrone”r o o souon. aos ce. r “ransormaon” reersoenseron o an exoenousonuceoeno exame, ae exoenousonuceoe mae manane as a non-nerae vecor,or “ransecn”a osrm “r, or aernave, maeneraenoeos ceenome.eerm nucec ac ansecon”sneneo encomass a convenonaecnuesornroucn cacumosnoaeos ces.xames oranseconecnuesncue,u are nomeo, an mcrone recaon, -exran-meaeransecon,oecon, eecrooraon, ce asas usc aeon none. -nreanv,eee.e.r,mse “erraonosoorumse nu,”c “seac acra snesuoermncee,”n aenra “eransnenc” reero a as an esomaasm as man osenome or “nerrans ane rou mueeneraons. ranscron o aocnrucoenoa conro”s aerm we unersoone arancaesa conruesoenaon o, oer serouenceeens onsen oera neo an eemen wc rocess “ wncer ocracnusrsa aoenra conro”mso aeserrman wsecr unone.rsoone arancaes a reuaor s useeren, a “v mecoaseenorme. acsno one or mor r” reerso aonuceoe seuenceesneonrouce nucec vecors,a e ce es.ecorsncue conn vecors, exresson vecors, sue aareneroasm ees n aa, nna oree rrovmaar ovc nees e ar, no ca oesns ese r eensc ao a smn maases nu “vaer.an”roens.aranroens errom emomens,e numer o eren amno ac resmueer o amno ac resues.n some ,,,, or.n some emomens, varans esrs a ano ou aoou ao,u,, a,,,,, ernave, or a ona, varans maave a seceeree o seuenceenmno w ac as. reerenc,eroe,n a onr nucec ac,s ee.e,.,n asra.eeorrm enxaem usen, va ara senueronceen as orn nmuecneoo, suc as aeas aou , , , , , , , , c ac maave , , , , , , , , , , or even,., , , , , , en w a reerenc amno ac seuence “e” reersoe a smeouuennc oe. reaveoeoa amoun aroucroucerom aee maeraor exame, suar were convereorouca oe susancea wouerouce a oeee susance rouce reaveo aeo.reocra exaeme,oo o e mae exresse as ooo suc as a suar were conv eee susanceor exame, a caron sourcencueucose, xose, aner aceeaoe.oo .onmn exames o caronee sources croora mcrooraon nns-s mnmas suera.., o ncacuurrarn o mcccurrororansms asescreeren areerveromaren occurrnaren n or w-e mcrooransms, or enneere, non-naura mcrooransms mrcrooransmsarouceoo s.n some emomens,e aon orooouceoo sn commerca reevanuanesn mcroa cuure wou mcroora c susraes.n some emomens,earen mcrooransms areuna nn sosmmse, e smuco asmeenass, mecroaorrenan msms. mcrooransms maeromeumscrooransms arerom sunomara.e mcrooransms maenumasomcocmocoa orasomcoa.or exame,e enusooorua,oosoro a, casscrooromcees, orerorooaes, mcrooransmse..,as ous, ororooomces.n varous emomens, oooruaoovaaomceouseas ces are seeceromoooruaaavae, ooorua a ,oooruaraocvovae,oooruaramns,oooruaauena, oooruaa.auena,ooorua saerocara,oosoroous a. coosr, mu renenss,oosoroous runenae,oooruaawanenss,ooorua arec au sarannos sae,e acneroomosoorooorouuas aa.e nvaaen sra.nn ceran- emo,menos,ooeru macraoorevaanesms - ,oooruaaevae sran -. sran -,ooorua ,oooruaaevae sran -,oooruaoaoevvaaae s srraann --,,ooooooruaaevae sran - ,oooruaauena sran - ,ooorruuaaarauocevnoav sae sran -.,oooruaauena sran -,o ran sran - ,ooorua oorua a.auena sran - ,oosor sooauesro aca.r ca sran - ,oooruaarenenss a. coosr - ,oosoroouso aos. nr sarnan sran- -,o,osoroous ooosooorruao moucus runenae - ,oooruaawanenss sran , an a maoen emnnna ee erxeanmosa n ae s csr c oan or manccr-oeo- wran esmm. o semceenss an o sera mnesoasroesucrceeoo s an escren..aenos.,, an,,. eren are oo s n a nurenero mwcro moreanumsmosrersocruceoeren naurarouceoo s, an maerown emomens,e mcrooransm secreen oeoo sn mcroa cuure.n some some emomens,e mcrooransmsroueoo snoe nurenrow meum.n nurenrow meumn varous emomencess, aeas aou oo wenrownne oo seecerom: a-roxa ac me mcrooransms marouce one or more esereo a suar acoo moe an aceaeo-errooxmao caron aomsnen acoo moe a suar acoo moe comrsn non-ese ac moe esereoe suar carox en o a-roxa ac moe a suar acoroe moer coxrous esereoe araoacone esereoe carox en o a-roxa acom morsen a manno or o aa ac an aoo eser am cn m soomeceu eem. soamnecnus,e ae s mucarro aorcoanos,m e.r.,o au Dc-emsa onnne or more s. s are e carox en o a-roxa ac moe, wc ma or mao n anor a D-arao, esereo esere roxrous oe suar acoo ma or ma noe aceoae aceae.e non- emomens,oosrouce a mcrooransm asescreeree as we.n varn smar comouns conann--roxa ac moees w varn cn maae a mxure o o aouo aou, aouo aou, aouo aou, aouo anouen, as,onue raone a m aoo oeu ues, o c oar an a ouroeuse.nn v vao ar a rnou n eemre ca oersm oon en usn. ssn ,a vua erran noonn e -enm sereo e ramnenes o,e roxor a- ouou- s o,r eo.x e. s,a unare ac a rcaone o e esereo acerous.n varous emomens,e suar acoosu acea o can aceae, o e,ara cane D-arnr a s noo omne-a or ec Lme -aroae amoe. .nns, someeo emoome snuar acoo moencues a caronoo, wc caronoo, wc cane D-manno or L-m s,eoo suar acoo moencues a acoo moes aace orounoe caraonno.n some emomens,eoo suara acsroxae aoson-romex car enox o eea ac.n some emomens,e rouno n.n some emomens,erox ns voanro- ma or ma noe aceae. eren, anorn auso emoom ceonms,o osneo onr msooraee ansorruorueceronm a a m cucrouorer oansem m ascroeosrcranesms asc seeeaceerom:: aceae :-roxa ac esereo D-arao w aceaons roxa ac e-serroexoa D- ac esereo D-manno w aceaons aceae :- esereo D-arao w acemaannonos w ace aceaons aceae :-roxa ac w aceaons aceae :-roxaae ac: ese-reroxo Da ac esereo D-arao aceae :-roxa ac esereo D-manno w ace-maanonnos w a aceaons roxa ac esereo D-arao w ceae :- esere aceaons aceae :-roxa ac manno wo D-m aacnenoa won aceaons aceae :-roxa ac esereo D- aceaons aceaes: ace-areoxa: ac- ersoxa ac esereo D-manno w :-roxa ac esereo D-manno wer aeceoa D-arao w aceaons aceae ac esereo D-manno w aceaons aceae :on-s arcoexaae a:-roxa arcaeo w aceaons ace c esereo D- a ae :-roxa ac esereo D-manno w :a-onsro axceaae :-roxa ac esereo D-arao w aceaons aceaea ac esereo D a-cma ensneor weo D a-cmeananoon ws. aceaons an aceae :-rox ransorm onuceooaoon o m e consrruocro cuocr onan ro ms ucm creoso ar naonnsms asescreeren maeransorme w a o one or more enoe -naura occurrn mcrooransm w aere exresson ca,eonnousenes anor exresson o one or moreeerooousenes. e mcroora uceoe consrucs anear seuenceoeneraenoeenome o enosmnu or a asm caae o auonomous recaonne mcrooransm ces. suc as eecrooraceoee.., maenroucenoe mcrooransm ces a meo muaeness on, -meaeransormaon,rooasn, or aroacerum meae anoc re.ransorme ces maeeece resence o a seecae marer suc as a ssance, a vsua oservae marer suc as asence o a caroeno, anor ounx noroor a reure meaocrouc.aenerans maeene seraassan ewon-seecve meaoowe screenn on seecve mea anor amneuncon ranseeonreenome ane recomnan e.., vaomerase can reacon . omoomouasnsaavenerae vaomooous recomnaon as ooseo non- aomoo eonus ronn cane enrce sne seecae marernoworamens suc wce aescnomnaoneweene seecae marerramenss reureor a cen onmn exeamraees oo seeceocmaee re mssaranoe seecae marer. ressancee..,romcn, nourseo ersncue an enzmearoves anoc reure meaocroen. rcn, auorescenroen, or an enzmearouces a asescreoneuceoe consrucorenec mocaon ooo roucn mcrooransms seecae mareren mancue: aromoer an a nuceoe con seuencearoves a seuencene mr,c wroeoreneromoers caae orvnene exresson oe con escreerensnuransm.n some emomens, aromoern aonuceoe consruc sruonn o sromeee emonoc o amnee ennsn,o ae eo m nouncr suoco eer noan e sesm e cuo. ennscreucno arorooucn aroenuecnnocoosue.., moc arooerasan asmorsonro ov aear, weecennceu sees:u aencreomoer a nuceoe seuenceasomooous c neenome oe mcrooransm a nuceoe woenr seuencea encoes aroenaroves a seecae marer an aermnaor, seeceaneromoer anermnaor seuences are caae orvnene exresson oe ne s moamree erm coonm seensu,enocennuceeo mcero cooransm. oo roucnos mcrooransmsrovnserucor exresson o aeerooousenen a con seuenceor aeerooousene an a nuc, wcncues: aromoer a nuceoe aroves a seecae marer, wereneromeoe con seuencea encoes aroen eerooousene an seecae marer con soers caae orvnene exresson oe con seuenceoreeerooousene maueuencesne mcrooransm. e nuceoe aacaeseecon or recover oe exresrerncue an amno ac seuencea “a” exames o suc seuencesncue as-a sesonrouc oeeerooousene.onmn consecuvesne resues, a -a seuenuceencae,or exame,avn sxo nne :, an a ca seue vn e amno ac seuence : nceavn e amno ac seuence erennr soommoee er,m anoomens, aromoeror an enoenousene mae reace w a enoenousene seuern ace,’ unerreansancer reon anor a’ mae aeoe exresson oe enoenousene oreea resn,ecreasn, or cann e reuaon orome enoenousene.or exame, aouanuocne ooee c soan o m asranscre an a’ anor an-ermnaan aoo roucsnrucoosr r mecraocon aromoer an wcncues: a nuceoe seuenceasomooouso aeas aoron oransmsrove, seuenceneenome oe mcrooransm aromoer seuence an a’ aa,reeene onuceoe seuencea encoes an-ermnaa.n anoer exame, ao annuceor a consrucor reacn aromoer an a oe roucnos m n a’ anor a-ermnaan aoo omooouso aceroaosr aanosrmsrove, wcncues: a nuceoe seuenceas aromoer seuence an on o aareeene seuenceneenome oe mcrooransm encoes a-ermnaa. aermnaor seuence, a’ , anor aonuceoe seuencea roven saom aere emomoomens, as sown scemacans.-, seuences are reace.ransormaoon coaunsoe ae enoenouseneoeae anorromoeroe en aene w an aererocmcoomer asneor usen a s marer ssem as sownn., romoer oeareeneaseen reace a neew seroumence as sownn., wereneermnaa. oer anoraseenuseo an- roven saom aere emomooomeonuss,o as se eonwno sceneomusaceaneonesa.e a –nor,erm seuences are r aeace.ransormaon cane accomse usn a s marer ssem asnnao.roe,enermennea wor o an aereermnaor anoree seuence as sownn., wereneermna eareeneaseen reace a newermnaor anoraseenuseo an- na s. seuenceoome emomens, a con seuence oeonuceoe consruce.., a con eos mr a seecae marer oror aeerooousenes coon omzeor exressonn erensrcrooransm.onmn exames o coon usaen a mcrooransm asescre , ,ove, ornae o ane coaones.nne so nmucee e oomomens, aeas aou , , , e secon mos common coonsneos mcroranes cmo.n seuence aree mos common or aeseue:oooonn uesrcaeneaeesorueoooonorueracenaevaeesueoonercen . . . a . e . . . . r . . .r. s . . . . . sn . eu .r. . a . r . . . .s.e.. . . . . ro . s . . . . n . . . e . u . . . . . e . . r . . . . s . . aeseue:oooonn uesrcaeneaeesorueoooonorueraceonruoeessueoonercen . . a . e . . r . . s . . eu . . .r . . . sn . .r. . . . . . a . . s . . r ... . .e. . ro . s . . . . n . . . e . u . . . . . . . er . . . . . s . . ere ex eren, weenr rees encsaon one m o oro en moeoe re enono oousene enousrsoenuec onr marcrcouoarranosmnusc aereoroev seeue ansescre susana, or comeeeee, sence,nacvae,own-reuae, or u-receuasea.ran, c oenreanno ecmeo oumene.s,., a nsornu-neau orare oecceurr enn mocernoooursanesnme a anseosrc areease orneen e conans aeas eneor wc exressons aere,n comarsonoe naura occurrn mcnoenous aren mcrooransmrom wce non-naura occurrn mcroora rooransm or a n some emomens,e mcrooransm conans aeas onensnmocsee oruvee. or exam,e,e enoenousene maenoce ou or ee omooous recomne.naon, enes arn z e sn soc em- nen ce emer n ,ouc erme eea xnse rs, e, or sseon mscr roeo.rucaens.mn c coonnaranss, a weeas one senceene.en comee eraserome oransm'senome anusavenenes arenoce ou,e are exresson o an enoenousene mae sence n neor eexresson.or exame, ansense oonuceoes, rozmes, or a -ase meoreen.ce.,,a sencn, s , aeen, sno omree ermooncmreeanses,, aenc erenasoe,e onro cusanenee see reueuncaeosn ouse exroe ass soes nu oerncaesa. encoes ene.or exame,eee maee auxn-nuceeron , an-e ormnea enusoenous uun, oreoacco ec vruserona on oraccner eonoeno musaeneenno aceos oun, seecncae e,w oa. r reorucerounc exonre asnsoonr sorae o non-naura occurrn mcrooransmroucn aeas aou, ,e,ve, re,sunne , ,a,ura, occu,rrn o,rare,n m,croor,ansm, , , , ane n , , , , or ess mcrooransmserve.or exame,e enzmenrom wce non-naura occurrn anor sorae o mae an acranserase enzmeee.os.,nacecawaorroucon ... oroso:ac cero acranserase roase en cero acranserase ... , ae..,ceroz-m-eoes..,aeosearoaeroasea ..., aeroenase enzme ereo. enase :..., or a sen , or aomoo rouconn m enaoeenonuosceen oeuo,r sreoncuec,o onr o re aunc eenznm een aosnecawaor caroeno emnaeroucon oe caroeno e mcrooranxressoneve, resunn reuce ororransormaone.., we or susana we coonsm, wc marove a vsua marer erveromermenaon, suc as s, mae weresu.eno a reucon, exraceoo sevesresenne mea.or exame,e enzmeneosneec oar ewmanae caroeno caroeno mae aunconacoene ccaseoene snase or..ro.uc,o onr a o a omooe maenonre c eo en. ooue,n souensceen,e or rae euncceoens e axnr eenszsomneeover,r roesuucnon on a a mn ecsrsoeonraa meaoe auxorocore meaoe.or exame,nocn ou or sencneenea enncsomesa-s .o.s.a, oer aecoamrooxoaseereo, reassuesn ... or cosneeamnase n enoenousenea enco aens a aunxo enrozmeaass rensvsano-uoroc ac. u,u, or, or aomooereo, maenoce ou, seonvcee, w or reuc rear, suc aseve,eremrovnomooou en exresson n enoenouseneas rsecnovmonaon. sence, or reucen exressoneve, rveneroxsomaea oxaon maenoce ou, oxaon oa acsane naura oecscuurrnnn m ac mrcrooransm w aowereve oea e non-naura occurrn mcrooransm ooransm oraren mcrooransmrom wcnvoveneroxsomaea oxaon mas enceorvee.or exame,e enoenouseneas ..., a-oxac-oero aeenraosxesoemnoa m-eomranreaase u enzunase ..., an ac-o oxase enzme - ..., a me roen , or aeroxso eroxsomaransor omooe maa ac ac-o snase enzme ..., or a sence, ornre re eon. ucoeenno euxsreesnseonaevse,n rveosuvennn moconraea oxaon maenoce ou, oxaon oa acsane naura occurrn m ac mroocrroaoransm w aowereve oea e non-naura occurrn mcrooransmserve nsm oraren mcrooransmrom wc an eno-o raase enzme ....o,r o erx aamomeo,e enoenousene ma encoe n enoenouseneasnvovener oereo. noce ou, se aaon ooos, suc as s, mae ereve once, or reucen exressoneve, resunn a mcrooransmarouces a mcrooransm onre or more oeoo sane naura occurrn mcrooransm oraren enoenouseom wce non-naura occurrn mcrooransmserve.or exame,e n somnee m emao encmoenes a, seecreeaseaeraeseoo s, or aomooereo. eromoeraseen aere o non-naura occurrn mcrooransmncues aenen wc exresson oe eno r reace,n oreroncrease,ecrease, or canee reuaon o e enoenousene.eonro euxsamenee ore reuaon oe sa o m asranscrerom recomnaon, , znc-ner n,uceearsoem,o orer ma.e reaceswae omooous enesuseo a seuencea encoes aee,n orenr soome emomens,e enoenous reuaon o exresson oe enoenousene, suc a ncrease,ecrease, or canee , an-ermnauson o uun, oreoacco ecs, vruus nomeo,e auxn-nuceeron n some emomens,e enoenous eonae. ma ene w aere exressoneve encoes a .n.n.o, ae manroneon-as-e enzme ..., a manno--osaeosaase enzme ..., an araooseareoeenasero enenase enzme ..., a D-xuonase enzme eroenase enzme ..., a-zmoseouc.o.no.ac,o anasueco esnez--osae osouconaeeroenase enzme ..., aosoucosemseomeras.e. e.nzm, ae- cer.o..as,e a ernaznsmaeoase. en.z.m,e , a.. s.n, aasrean esnzemoea,se an en aczeme-ranse..., arac- ..-, aon-cana-ac aaroxase enzme, a rans rase enzme snase enzme ..., an ace-o caroxase enzmorroen, aa ac eroenas or aere exoe rm e e ..., or a maae n sesenz s eomme n oo anm eenn.s. o, a. e nnoon, u- o snra a eunro eamo , as oocceusrcre rnreo e m.cerroeonr,ansmaaseen moe enoenousene or aarcuaronuceoe seue e.., moe suca an eee, sence,nacvae,own- ncesara, susana, or comee er o one or reuae, or u-reuae,rouces anor secrees aer aren mcroor moarnesmoroom wsc, susce arsve.osr, exaamnee, naeuroao occurrsn m macroeorncarneassm or aeas aou, , , , , , , , , , , , ,e , , , , , , , , , , , , or , ore , , , , mc r,n comarsonoe naura occurrn mcrooransm orearen errosorraonuscmerom we ncon-nea nuorna-na oucrcaurrn occ murcrrnoor macnrosomr caannsmeserve.eoo , , , , , , , , reaeran an o aou .eoo ersrouce e non , , , , or o aou , aou o aou -n,a aura occurrn mcrooransm cane aouo aou , aou o ao ou o aou , aou aou , aou o u , aou o aou , aou o ao,u ao aou , aou o aou , aou o aou , u o aou , aou o aou , aou o aou n some emoo aomuens, a no,n o-rn aauorua oco aou . aere exresson o an eno currn mcrooransmaaseen moeor enoenousen enousene, asescreeren, e.., moe suca an e e or aarcuaronuceoe seuencesara, susana, or comee moereeo, soence,sn,a scucva aes,owns-r,euaanee, o nra uur-areu ocacuerr,nro mucces areaere o one or mcrooransmrom wcserve.or exame,e rooransm orareneas aou, oo es maencrease a , , ,, ,,,,,,,,,,, ,,, , , , , , , , , , , , , , , , , , , , , , , , , , , , ,, ,, ,, ,, ,, ,, ,, ,, , , , , , , , , , , , , , , , , , , , , , , , , , , , or , orer,n co, , , , , , , , , , mcrooransmrom wce nomn-naarusorano occeu nrranura mcr oococrurarnnsm mscroeorrvaen.sme oroeoaren e,s.rou,ce.,e. non-n,au.ra oc.currn, m.croor,a.nsm c,an.er,ea.eran, a.n o, a.ou. occ,urr.n m,cr.ooran,sm. m, or..eoo esrouce e non-naura . , ae an o aou. o aou. , aou. o aou . o a aoouu..o a, aouou.., aoou a.ouo a.ou,. , aou.o aou., aou o aou., aou. aou. o aou. , aou. n some em o aou. , or aou. o aou.. or aere e omens, a non-naura occurrn mcrooransmaaseen moe enoenousxerenses oorn a oa arnc eunaoreononuusceeone,e a sseeusecnrceesearrean, e,. su., msoanae, su ocr coma aen eee, sence,nacvae,own-reuae, or u-reuae, aso exresses e seecae marer, suc as an enzmearoves anoc ressan aeerooous romcn or nourseorcn, auorescenroen, or cee.., ressanceo meaocrouc. an enzmearouces a reure xresson oeerooousenes een moone-naourr eaxr oecscsuorrnn o ooneo or moreroeuecrono moucsrooernean sesmuse anrcee.rovee non w-nacurave occurrn mcrooransmsncue one or more exoenousonuceoesa a exresse one or moreeerooousenes,.e., one or moree encoe an seuence. erooous nuceoe con exame,x exrersesssonon o o a aeeereoroooouosuene seuence ma resunncreasen eraaon,or xresson o aeeroooussernac-ceroase enzme , or aomooereo. suc as s.or exame, one or moe seuence mancreaseosness ooo s,ranserase enzme, aon-c re o aeerooous snase enzme, an ace- masnro a,n ora a-ac aransaorrrooxeanse enzmee.., romsao exresse o , or aomooereo, mae exame, onxr o er oeve rs msre oox rnr e oes asee.erooousene seuence mancreasea ac sness.ororuoes, ace coe o aeerooousa ac snase enzmee.., , e..,rom. mae ex nzme caroxase , or a mac enzme, or aomooereo, nresse. encoes ar saocme- emceroomeanses,, ae mcro sonraanssem, a enx acreesse-sra onnsee orras meo,r aeoenne-c seauencea aaroxase, a ransorroen, aa ac snase, an ace-o carnoaxa-ac enzme, a mannoeroenase, a manno--osaeosaase, a manno--se eroenase, a D-xuonase, an araoeroenase, aucose--os osae eroenase, a-osouconoaconase, a-osouconaeeroenaasee, a oro asomoouocosesomerase, aransaoase, aranseoase, or a maaeeroenase enzme,or exressno sno omeere on eo em. oro mmoreense,e aro noon-onuasureane, o acscurersncr mecrooerreann,smrouacesa asneoern s mecoree reororearn o one or moreoo s, s es a mc uc as s,ane naura occurrn osrm e oxarmareen, mecroooransmrom wcserve. , , , , ,o, ,ers m,ae,ncrease aeas aou, , , , , , , , , , , , , , , comarsonoe naura occurrn mcrooran,sm, , , , or , orer,n non-naura occurrn mcroor orearen mcrooransmrom wce naura occurrn mcrooraansmserve.eoo ersrouce e non- , , , ns,m can,ereae,ran a,n o ao,u o , , , , rouce r .eoo er o aoue non-naura occurrn mcrooransm cane aou o aou , aou ao aouou , aou, aouo aouo aou, aou, aouo aouo aou, aou, aouo , aou, aouo aoou aou, ao,u aou o aoo auou , a, aou o aou , or aou ou o aouor exressno sno ome a emo eeo a roomoueonuss, aen neo. ,n a-naura occurrn mcrooransmaaseen moe marer, suc as an enzmearovess anescroec resesreann,c eexer.es.s,e ress asaeneceroooousro smeeccna ore nouerseeoerorcono,u as sueoercesaceen maroreern, m oar ane e enxzrmeessea aoroneuces a reure meaocrouc. eerooousenes, suc asene seue orn comnaon w one or more escre nces enconroenroucs, suc as enzmes, ne sreomn. or exresson oe a emeeoroomeonuss, aen neo,n a-nsauersacr oeccuerrrenn, m acsrooo erxarnesssmeaaseen moe seuencea “a” seuence, wcs aeneoe amno ac ses an amno ac rouc oeene seuence an wcacaeseecon o uence oe exresse oeeerooousene.or exame,ea r recover oe exresserouc nne consecuvesne re seuence mane as-a seuencee.., sxo :s, oru aes, aca se-auen sceuenceavne amno ac seuence :. eavne amno ac seuence eos o asescreeoro esu re ac nren .ronvo e oeo r moorrs e orouec nnon a-naouroa occnur arn non m-ncarouoraran oscmcusrr mna mecroroorwannsm mcueuurme, unn aner e cnovnronomnesn,a su acre a ssu aaoereoarcorro,wa o conea mnsc aro nourraennsmrso awn moesunmecsuurencurcens, nosronenes sosu orceos,onorasnc susea mnccerosore.an.,s s, sou nmosr.ance s causur,e a mne anum oncerues caron reureorerow oe mcrooransme.., vamns, amno acs, ec. susances ca, one or moreoo se.., one or m . roxa ac moero oreoo s seecerom a- an aceae-roxam aco moe car eosne aomsnen esereo a suar acoo moe moe comrsn non-esere roxrourse esoere suar acoo moe a suar acoo ac moe a suar acoo moe comrsn a mannoe oro arae coarox en o a-roxa caroex m ecnroo ora ans-msrnoxoae cu acure m moeeum a,n an a moao ees reecro ove areaac ro amcone esere e meum a.reo n se sce ormee emomens,oo ssuc as,u nomeo, s e aou , , , , , , , arerouce a aer o aeas , , , , , , , , , , , , , , , , , , ,, , , , , , , or .e meo maeerorme as , , , , or , , emomens, a “connuous” meos aac,eac, or connuousrocess.n some cuure meums connuous remove u ase,n wcres meums connuous ae, we voume reav e same or susana same rae,eene cuure occurrn mccrae oor, co aons nsoan. msesscrseuc as,u nomeo, srouce e non-naura mo aou.m.n some emeroenmeanves, aeenos o aeas aou.m, e.., aou. e cuure meum wouss oe mcrooransm cesos mae recoverearveserom mae recovererome cuure meum wou exraco.nn w some emomens,eoos emomens,eoos mae recovererome cuure m ane oranc soven.n some searaonecnue, suc as,u nomeo, cenruaon,ecanunm usn a mecanca orassve s e.., connuousecann, non-nauruaree orn ccur.orrvneos aooreacrooru ocrn o merc mrocroa cuure envronmen wcncues a row meum.eoreacor mae oerae wornan asma asescreerenn a nuren n some emomens,e mcrooransm cuurencuc,eac, or connuous ssem. sourcee.., a mono- orsaccare, e..,uco es one or moreroc caron . , ammonum coree..,. ,oassse anor sucrosee.., ,eas exrace.., osaeasce..,. , manesum suauemexaosraae monoasce..,. , soum souon conann varous sase.., m.n some emoeme..,. , an mcronurenncues anron sa.usraveu nonmnron sasa mens,e mcrooransm cuureron core ,ron suae ,ron nrae a,roen useosncauee, wou,mronaon, aucmeaarae,e,nrone er aenae,roruosn o crraeer,ronra meaa sea,erosn, a onxa oare,anroonmeararace c,ormone suxeccsnaeere, anron exame,e cuure meum mancue an o.or m ron san a concenraonne rane o aou. some eom aooumens,, ee. m., acroooura mo aou., or suc as aou. o aou..n sourcee.., a mono- or-sacnsm cuures suemene w one or moreroc caron aou , , ,care,, e..,u,cose an,or sucr,ose a a, concenr,aon o a, oreasn some emomens, one or morerooc caron sourcessncue, suc as an o, an a. aa ac, aa eser, or a mxureereo ane, escreeer meenno a m cuaurenc mueeu cmuurann a. cuoesu oaneon or o m noon-naura occurrn mcrooransms as caron sources.n some emomens,e cuureoes nornecuroc e.., non-rooc oer emomens, cuurencues one or moreroce..,e nrooc caron sources.n an one or morerooc caron sources.n ceran emomon-rooc caron sources sources ae, e..,urn an sae orowncun exonenenas, arowo,naroc caron o mcrooransm ces rea an aereouaon n varous emomceenss s,aeon varase ,,,,,,,,oume oe mcrooransm cuure meums aeas aou. n s ,, , , , , or more. . wvomoe a eomuomewnvs, nreo cueure conansessan aou wv nroen, or aou ammona, ammonum sa, nrae, nn.or exame,e nroen source mae seecerom urea anservaves, an mxre, nuceoes, nuceoses,roens,ees, amno acs,wv amm uresereo.n some emomens,e cuure conans aou. no vnarumn core. concenraon o emomens,e cuure conans one or moreroc caron sources a a , or aowuv..n vawrovuso e amooumensw,ve, e..,ro aouc c.wvo aou ,,, monosaccares, oosaccares,osaccares, suar aron sources seecerom esers oa acs s, oranc acs, esers, aee asc,oeoosn,eso,os,oose..,oo maeras,noceuoscrosaes,nusra co-roucs, an acoos, wase sreams,an caron source mae a monosaccare, an oosaccare, or mxuresereo.eroc or more suar moees,or exame, seeceromucose aosaccare wc conans one aranose, mannose, ceoose,aacur , sucrose, xose,aacose, ramnose, n some emomens,e caroonnc ac,acose, soorose,cero, an mxuresereo. aou:, aou:o aou:, aouo n:rooe ano rauon:e, a cuouure m:eou ams aou:oo aou:, aou:o aou:, or ao ou:, aou: c u:o aou:, e.., usn a nroen sourcea saonmee e cmonsume or uze e mcrooransm cesorrow anroucon ooroucs.n .o aouom°en.s,e mcrooransm cuures manane a aemeraurene rane o aou° oo m orooucs o arn mx coumre ooswoon osr moreoo s,roucen an oe enneere ecsrcororeansmsescreeren orn an oe meosor cuurn e mcrooransms as roucene are nonn, arerove.n a reae asec, comosons areroven wcoo s, s mancue-naura occurrn mcrooransm asescreeren, arencororae. eoo roxa ac m aone oroemooo casreosnc aroeeren, suc asoo s seecerom: a- an aceae- roxa ac moe eseremsoneen sua ers aecroeo moo a suar acoo moe moe comrsn non-esere e a suar acoo a rox rous esereoe carox en o a- roxa cacro mxoe en a o su aa-r acroo moe comrsn a manno or araoacone esereoe n varous emoomxenas, aeco mooe a cnon aanono co emseros oo ansa a ac . aeeren, a suracane..,or recover o o, a wen aen re seecerom a ceanser, emoen, asersane..,or ceanu o oncun see,r an anoam aen, an emuser, an aen, an anvra aen, an anuna aen, a sermce, a oeum, aumecan, an anacera crsa moer, annsanzer, a vscos moer, a m nnsecce, aurcan, an aesve, aoam, a mousse, aoon, aam, an an onmen. xn enn a, a reease aen, a cream, asree or susanaree o an rooc caronn s soomurece e.momens,eoo comoson mcrooransemrvaves oeoo sescreeren, anroucene non-naura occurrnnvove mocas aonn meosescreeren, are asorove.or exame,ervaves ma acs, D-manno, D- oara eoer, ane suearr acoo ore moe, oro,ncun roxaea ororaecaonos. ervaves.onme exames oervaves areescrennc , , an , a o wc are maon,oueseo ree oorence an cnoemren usorsn a cone esr e ansnn ers ures aees nn. neuemrereonuss, aexceas,o ansr,ocnceumcna wou conro ouna annsecess,oorocessn suc as ceann aensorress a snucro as arusc,a veonesancesu, mneasou ans,roacseassse anoo emsu,sooonsrocessn suc as reooc moersznenooo suc as maonnase,ressns, an srus, aorocessn suc as anaerens,oocemcas,eroeum exracon suc as reease cereanmscorracn, consrucon maeras suc asurcans anemon aensorrc,nusr,, c ceomsmeenc an concree, mnn suc as auvansne coanusr,u anaer su s suc as creams,oams, mousses,ams, onmens,ersona careormuaons acen ass, searameouosc,s souc w aass oensm, ceonns anone crrs, soas, creams, snreamens, an mosurzn a eams, sermces, anacera, anvra an an mcoarenc ceorm aeenes c,oemauesro anu,xaorrem aeenas,onue o o con emamusnaceao snoos,rmrouronvewa aerom anza suorna,cee waner, caussa sue areusesoounsn em munseosn asnoruaerr meas,n rueaecausere a oe enxsoosrv aess,anreruces,acaon o an oeocemcas suc asoese an aorm cemcas. enn mea wornus, oo comosonsroucene enneere mcrooransona nonmn uses oe areescre, e..,n..aenucaonos. m ans an erese,no me oos arencororae reerenceer wc eoown exames areennenneer eonuresrease.,u nom,envenon. xeam sraen.ransormaon o oooruaaevae w an anoc marer exe oooruaaevae - was useoreransremraesnea woreensecr exere.ssee carosmse aeooo>runaa,o wruoce cosnraonmsoeerourse,o warsc an-aceromeasmsrovenora, e a., aen sco _ .e seuence was muaenze : no a remov ceosa c,osm, ana ses an orere sneszeromenewz easm us wnasrea ureram snorereannuscooerrm seaeoc onae arroasum ocn. me arasnee uasr anmrcmon acrossenser o anneanme,o ans wer aen rnuena anem reearcauorn: e, s azne a ers :.eac n wsn o o exemensaoen,m.e. ororxmmearse, as o aeo,meenrasuer cean us renacsoonroano warsecreaaroen aner r reeascusone.neen wa wear.s cec coenceorur on was measure usn secro nraon oransorm oomer usn aanoro. orae e a., . ces usn eecrooraon a smar meo was use asescren sne coon was e sran was sruc ou oneaseoneexrose mea,en a cuure wasenancoc-uaenom o anncuae a °or aroxmae ours.e unerese cononsuee srannoasm o mean aaeas anrown uno ase ces a ocaens weree aeoeu anmex oo arroxmae ours.m oo-aseromson on.es were resusenenm o. mnues a °.es wereece co voume anranserreo mcroueues.es w ce co D-soroerm o orna own a xor sec.erena was,ere o wa.se soxr wo w.as soro snnn ee.eee wasen mxe w o waer conann aroxmae ae oora resusen e anranserreo a.cmce co cuvee.e ces were eecroor nsormn eneuser a. , oms an .mmeae aer eecrooraaeon w, ce as woera roesusmen cee cunurmeu oe asn,ceac ceon m axnunrecu oa:or a. s,orrom an. aosw mexuore re wcoavserraone rser.re eaes wereeee, resusenen oeas exrac-eone-exrose , anen meo ones a aarro wxm m nourseorcn.aes werencuaeoras a °.s .aevae wasaeransorm coeon wormnenar uns en oransormn . aove.s a neave conro, waer was susueorceo amn >na usne meo uen a: uon seres anen soaen roecon.er recover,e sran was eren concenraons o nourseorcn.. er concs on aar suemene w erenceeween cesa wereranso enraons o nourseorcn, a cear anoc seecon marer was vse.arme anosea were noransorme we eermneoe sucenor seecon.se onsaa, m oourseorcn was xame. esn an assem maroerr erxanrsesosrmonaoorn an noc-ou s anoco re csosnsruc a consruconoc ou aene, wasesne sucaenernaoe caonce cassee >nasane seuencesomooousoe reons n orero onan seeuence oeene sucaeene seuencessrue.s. – - sran.. somooous seuencesomoo arms, we seuenceeenomee a seecae mar ows conann seuencesomooouso aenomc reonannneraon erns case a nourseorcn ressance cassee >na.. sows omooous o receomeenraooono.uswoas amnosr w reemreovrae oaree eonr eoacenoeunse seoueencneo,c aceco omu, wse e uasecoa csrmeae conneaarnn onreomomeooasm arms a snua oeorer saenescoromna moanr.er.omuooseouusen re, was eweene s reonne seecae marer seecsor cesaave as comnaonransormaon cassee weenome.. scemaca sowsenoo recomnee e seecon cas mc seuence reace avs.oer sreannom wes as seee sru. uecnc onu, onee sarsane-one weas oaneromea coecon anocuaenom o anncuae a ° ovxerrnose. mea,en a sne coon was uenom o mean aaeas anrown une soauraaese. cuure wasenac- wasewomesnse waer . ocaens uns oo-oaseas cee cse wse were resusenenm soro,.2 soum c re mercaoeano , ..e rae,. , an. - ° wene san,enorourss w wereenm oesem oovearns w m ocase a wasensoaTMeorour a °.enomc e sran weas usneaserureeas . enome was ass seuence usn a comnaon oanoore anumna reas.e unnnoaeeemnee v. us.n. e anon, anenerecons wereone usne an e seuence oe ene wasenease one annoaonsenerae aove . s usnnee-uaenerom.oo aruorees aseuer seuencenro eenomc receo encoe ns sracnesrrooveenn wasene:or-. e seuence oe ene wasene us . enomeroe ne enerom.oruoes eneor-.eennomc receo e:nc.oe snenusa sransrove was :. n mouar conoc ou eerenen- wasreare oenae assem usn a wsaonens sseem.acar moue wasane wsa ses suca wensese oenae assem waserane sc ensa are aroraeo assemeeasm. manuacurer’snsruconsso.rme usnesa assem rom usne anamcanamcn seecaeac-one.oroenae assem was creae sne conn ressanceenenowo searaeasms suca oneasmn an o recaonanee’ seuence oeanamcn ressanceene an ao orn o ene.e ane seconasmn an conanee’ en oeanamcn ressance consrucearosmmsesnecueannrmernn ses an suca aasmsramen coenaansmnnasm e oranns cou o reoe ame we caon ananamcn r: sam ess we aansr ce cmoenrss.ruce orern aene aroraesa sesromwsoscences :.eraemneenramenane e ws aaersncueese aaers were suseuen useor c was orere w eec, a commerca avaaeasmrom , was ameon unsn. oeoansm : an :, wcnrouceeuwcesoesoenearze oramenco se aaers were asseme us ecae marerromsacone.e suseuen amcons e seuennce anan assem u:sn we manuacurer’snsrucons. a coramenco seecaeacon as orereromwsoscence coneno marer wnas orevreomnorovweoee rcaese o oe. n soemaoraoeousas remcoms.naeorns,rae nmoeurseorcn seecon : conanseromoer ane’ seuence oe nourseorcn rensna_, cone weeomoo armoreenearee.e seconramsanceene ans : conanse’ seuence oe ressanceene aneermnaenorna_, e r omoo armoreenearee.e nourseorcn ressan ans cone w ars o sare seuence, anusomooous recomnao ceenesa aseuncona marer.ese seuences were orerero neweenemes ano a coramenco seecaeacone. mwsoscences asasms cone w-e soemoueonce arom rsemaorveena an asna cu se wsere s rannoemsz meua won. mnu oaroenrs reaveoe sruneuncon o aacenenes,eomoo arms werees o avo muaons reureoromescaon were on aensee ne suca anareeorsruon.omoo arms weree con seuence oeene e cener oeenene ev sne sucae remove aeaswo exonsn omo en o successuomooous recomnaon.e seuence oe assemo a arrmsor sruonn- wannsa ses enan suseuen :.ore:n,-e are:- :, ann: a-n- assem u s: seacer. o senoucen ocuen or sac.ere seu : wasncuen eacasm a coramenco seeca ences were orere asasms coneno asms useoer assem coesa wceroneromwsoscences. resusen e mnree usn sanar meos ann-.weon eo waener.ae assemes wereerormeo assemeeasmsor nocoun,n,nrame-ns useo assem,eneeas smacer, : were:ramens useo asse an na.e na,nmee r asm : were:n,n, mar,wooen saeac aesrs,e amnes wneree-rormeo . nocou.e ramens useo assemeeeasm assemeeasmsorn,n,n - ,n sacer, : were:ramenso assemee r an na.e a,n sacer, anasmn - :. were:n,n,n on seuencesxoarmeeero.oous exesresnsoonr were o exmrezsson coon usaeaeeermneromeenome seuence o en se usn aacaee sness oe con seuences, w .oruoesae.n orero seuencesreaeranasears e secen seo avoomoomerc enzmesorsa , ano removee reconon sesor resrcon x-,-same,a, a cnons seoacae mouar assemecnues. aconeane a ses uence was orere coneno a coramenco ronromoersaoro nmowavseeorseccencoemoooe :. ecausee mnmze unesrae recomn osenome areesrae romoerseoe sucenorve exaon weosenome.e souoenoe comae w a mouar assemreecssnonu oe, ceerearono muouasonesnees.n. a re nmeowvao os.oereover, s oesrom mousersee mraveeorome servoemraoe srseceas cou aeceruncon.ereore, weese a vare sron exresson o ne ooooruaoenromoersa suore exresson o sran-.eow, we reor a seuencea suore e exreaecreooouse one ssenuensc oer uanssm. romoooruaawan ream oe sma rosoma suun seuence muaeo removea,sa aenss :.ac seuence was ranom seuence nsm resrcon sesromeromoer anermnaor coramse.ncoes see seecuaenecesac weroene.en oer seereue sncnes wesezree wsoscencesno a sesor suseuen assem. an we orereane wa resrcon romoer ane ermnaor re re use ase overanseweene s aermnaor,e ermsecve, enan a seamess assem. : wa naorromoooruaoruoes srue, wes use e co e.xonreesss aoren coassee wasneraenoe ocus.en s e .acon rme, aownoraceencaon oe onareneraon o easm eor: exresson was consrucene same wa as - co coramenco seeca, eexceasa raerann acer :, a use.sacone -m conannenacone waas croou : was n,n, onsruce usneasmsorouce n - ,n aroou, an na a-ase-oenae aassemroo wuas useo co:ne as.-. . exresson consrucno sareasm cosn ex seresusennce were ass:emee wermneaor seueancceone : e romoer a seuence : o : ane a rouce :.onn wasone usn ,s asemn a reacon conann o aseuer,. oa- enzme voume on..e re oa ase , aon wn o eac ramen anor anaor cces.e resunco ans wseamsen wa cscreanseorwmeeenno mnues a-ea ° an an seu menncuee vse ar ° aove. e as xame.noc-ou ransormaonro om.aevae-:ro an o ucn anear amcon: acro wsassereareor asm va usneueroaromerase.ermers werenser oe : an :.omooous recomnaoneweene s rermoenrsne seeneocmae.e marer seecsor cesaave aso recomneeransormaon cassee we snase,earecneaerosunc oe caeroenoocouss,naerss, aunconacoene ccaseoene srue, ceso noroucee remenasawcaaneoooruaenus.s ereore,roves a sraorwar rea seennooorua coones.ocus vaomooous recom -ouor weerransormn neraes aaermenaon naon.oreover,e caroenosrouce eeasurno unes arerooc anus seueseren rouce e srans.s canea sranaraoar cooraon oe resun .us,sesraeorouce rom a wasransorrmoexs em noaneave .a. suc eva o co e ano seraa sron. ownnroms e.ac-as.me oarsene ocus o- coonesarew on aae, aroxmae were w ervea ou o aroxmae coones on seecve mea an oserveae co es.-.e resruce encone ocus was successu rorenoe was sae.o conrmaerome nocou sran usnrmer emove, we ameenomc exrace .erme sa am eer a reon o or . an rs amn : ne : no nocou sran amc:e ono a a rnn amcon, werease e nocou : rmersee an -°. sran..e resun sran wasanen cero a near orransxoarmmaeon. oe.eraooevoauese-ne e wxasresrsoon : usn wrmers : an :uc aerom ceane u w amo sescre aove an ee oe n ean anoncenraor an euen waer.eseasms conan o ourseorcn seecon ressanceene an aeomoo armarene asmc cuosn.annseare r was oroucerom :ne same wa.sareneeneoe e nourseorcn ressanceene ane r omoo arm aon an. o romeocus.or eacransormaon,. o romeeasm e ces we r asm wasransorme asescre aove.er recover,emeraurereor aaero oxnmae sue am wence won we amn o re no cuorsoenoesr wcenre an vsnceu oanee a raoeo.m w wasen ccouonaeronm eacorranso arma°on. was re wsarsu vcsu oanze aa ma menac,aoenn u as snn ane cocon croscoe w a er se w a.s exosureme.s a conro, a we coo o ransormaon w an , wcsruse ocusuoes nonnrroouuccee uore wscaesnmcea, weereas.e. coensro cona nnon.e exresson cassees sowereen romasms xame.: nocou usnrmers : an a:n an ceane u as:escr weere a amove.e r aosxmeascere. ao ove e.aco c oece roersunenranoena orraem aennso wecre resrasnasormeno.aevae- ses ormer nce marer a ,ree am an ~.s wer see uusee: : an :, wc :nce, a wcrocss amee ao ~mo.o s aermu,enc : an enomc , wcs remove aerneraon enernaoeomoo armsne osse : oe anoc marer ae ocus, an acr an :, wc am a ~. seuence resrucu r aaev weo asnm uoo sco eou a o sr nrm oa. cnusa wu eerreem re os.ruc o ann a mea. sne coonrome enomc wassoae usnemourocwnor-ours.snm o cuure, manuacurer’snsrucons.e wasen screen eaean usne uerosaromerase usne manuac e usnermers aove usne osve amconsoro urer’snsrucons.evera coones wca , an wca aosvee aem anca ron s, wcace amcaon oe nerna e resun srans wereanen oceroe a -°o.cusrmers, wereene .. xameee. ceumuorness wraereon s oareor re sauceoans anermenaoenmnorcouvaemnenn oeca sran socsonro w w-e.aevae- ero mea a sran ane- a srannom o encu-anoar sr-an woausrs cu aure°noreacorues. ara e a., usnm o mea w aonram wse wre-e-nea asescren mass saeass a° an rm o aaor oucose as a caron sourcen use.ucose consumon was m n. nocuum oe see cuure was row,ucose was exa onore usn auceevce.er aroxmae o ucose remaneassusen saeass conanne w-e sran,u. o consume.cr conanne- anocou sran, an was nooneren susana reouras were coeceoro srans.e- a sran sowe roes vs ce accumuaonn comarsono w-e,ase one sze oeromaraene mcroras.. er was measure usn arooco aae rm usn e a a. m,ane.cr ser,arroere voouumr,e as oow eeo a sceeaeeo wrere m anuees,o aneaesns, smrr oe ae e evao arcaeeaeo s mueearsnuareane waosa remeorve ono arroe-wucee.eeoroscaeue.e e aceae was rouce an averaeer o. an. o , re ws-e ana-srue sran erram oucose o. an. , resecve.eecvea ans ae orams aroxmae more erram oucoseserenc rue sranrouce ecwo same-es,=. .. en was sasca sncan eroenx saemueence.anroameuerneeosaosrum meaosnecawa : was useouer aaaase oreceroensnoromenu.manro omoos usn . sneroen : was reurne weva aen- vaueor . aansenroaaaseeneomoos osroena are anno o.e- “erneroase oman-conannroen”noooruaram ae as en anoooruaoovaa , ns ,. oocae aona canaeene . en. was ae, wceneuaveosns,eec aormescrenone e a.,eves o snen.e ene cusersase on unexece conserve cusersnvovenuncoonsan anensosa.ownosnuaev ceusoesrsn weerec ceuns eexrasm wenreeoenosse omans conssen werooseosnecawaor aseesncree w e a., nara roene.rs, arorooesne an cnuosaere co ansa ans “ae s aoce coro oxaese”-roea ac snase aa , an aroen annoae as a “sero-nnroeneserase”rn: : , w oerenesne cuseravn no osense reaonsooen s: : enes couenvoven: an a- rouoe ac-oerveness.ese osness an ormn an eseroneweenea ac rom cenraa ac resecve a anooea o , se.con c:user con aaennse: ann aoaenee a ansn aoaeco as a mannoeroenaseroen: : an aene annoae as aonearnnes oranseraseroen: :.eseenes couenvoven: ero-acranseraseroen: eseroneweeneoo anea aca anucon ooos eormaon o an - rou onea aca o . aceaneooea anore an exameosuoruerooreonnvenonaseenescren someea wa ousraon a ceran canes anse mso o ccaaron os m unaerseanracnc,e w woeu aeaarernnoromose se ser anne sc aore oe coennsvreuneo ans, wmcnsee snceoaee oneen avenenone cams. ereore,eescron sou no reerencenuecra enonres,esaeonr as, anuroaseesn a anoc.aons ceeren areere ncororae aenen,c oer.aen a ca e same exen as eacnvuaucaon, reer on were secca annvuancaeoe soncororae SFELAGIDtNO:1 DYKDDDaDgK SME IDNO:2 EycKLtIagEEDL SIE GnGsAeI CrD Ct N ATfO Cr: To3 GmAAPTLC0A1T1GCGpCTGUCBT2C>TnTaCtAC;GAcGoCnGtAaCiGnAsP1,P4bindingsites GCTGCATCGCGTCGATCGCGCTCGTCCCCCTCAAGACGCGTGTGGGGCTACCGCTCGCTCGAGCCGACGCGGT GGCGCCGGCGAGCCCGACGGCGCCCGAGGACGGCTTGGGGCATCGTGCACCCGCCGATCGGCGGCAGCGCGTC GTCCAGGTCAACACTCAGCAGCTCGCGACGGCGCAGAACGTCGGCGCAGGGCGACGACGGCGGGGCGGGCGGC CCTCTCGTTCCTCTCGGGTCCCTGTGTCGAGCGCAGTGCTGCTTCTCTTCTGGCGCAAGCCTGCGGTGCGTC AGGTGTGGTGGGACCACAGCACCGAGACGCTCGCGAAGACTGACTGTGGCTGTCACACGGGCCCTGCAGCGCA GACGCTCGAGCTGAGCCTGATCTGAGCCGTCGTCGTCCGGCAAGGAGGTCAAGATCTGGGCGCGGCGAGTGTG CCCGGTCGCGATACCCCCCCTTTTCCCTCGCTCGTCTGTCGTCGTTGTCGAGGTGCAGGCGGCGTGCAGATTC TACCCGTCGTATCCAGCAGTTCGAGTGCGTCCAGCGATGTTTCCGTAGCTTGGTCCGGCTCTCTTCTTGTACA TCGAGGTTCTCGACTTGGCCGCGACGAGAGCGAGGCGGGGCGAGAGAGAGACGGTCGACACGCGCCGCCGGTG CCTCTCCCTCTAGTCTTCTTGTGAGTACTCGAGGCTGCTCCTCCTCCCCCCTCGCCCCATCTTCCACCTCGCC CCACTCCCGCAAGCCACGATGGCGGCCGCCACTCTTGCTCTACGCCAAGCTAGACCCCGACTGACCCGTCCAC GGGACGCCGAGGCCATCGAGGCACTGGATGGGTCCTACGACACGGCTTACCGGTACCGCACCAGTGTCCCGG GGACGGCTTCACCCTGCGGGAGGTGCCGGTGGACCCTCACCACCGACACCGTCTTCCGCGTCACCGCCACCGG GACGAATCGGACGCCGGGGAGGACGGCGACCCGGACGCCCCTGACCAAGGTGTTCCCCGACGACGAATCGGAC TGGCGGGCTTCGTGGTCGTCTCGTACTCCGGCTGGATCCCGGACGTTCGTCGCGTACGGGGACGACGGCGACC GGAGCACCGGGGGCACGGGGTCGGGCGCGCGTTGATACCGCCGGCTGACCGTCGAGGACATCGAGGTCGCCCC GGGCACCTCTGGCTGGAGGTCACCAACGTTAACGCAGGGGCTCGCGACGGAGTTCGCCCGCGAGCGGGGCGCC TCTGCGGCCTGGACACCGCCCTGTACGACGGCACCGCCGGCTATCCACGCGTACCGGCGGATGGGGTTCACCC CTGCCCCTAAGCTTATTCACCTGCACTCGTCCAACCCCTCGGACGGCGAGCAGGCGCTCTACATGAGCATGCC CTTCGTCTTTTGTCGTCGCCCGCCCGCCCGGCCCCTCGTCGTCGTCGTGTCCCCCTCCCCGTCCGTTTGCCC TTCTGACGTTCTTTCGTCACGTTCTCCGTCGGCTCCTCGAGCGGTTGCGGCCCTTACCCCCCACCCACACTAC GCTCGGGCGCGCGCGAGATGGGCTCGAGAGTGAGATACCCCCCTGCCAAGTCAAAGGCTGGTTTCTCTCGTCG GGCTCAGGACTGGCGTCGCAGCATGGGCGTCGCACGCGAGAGGAGCAGCAGGCCGAGTTGGCTCGGCGGTCTG TGACGACGAGGTCAGAGCGACCTTGCCGCCACGCAGTTCAGACCGTCTGGACGTGAGAGGCTCGGCTACTCGT CCAGGCGCGGTGTGGCACTGCCTTTCTCGCGTCTCGTCGGCTCTACTTTTCCGCCGTCTCTCGTCGGCCTCAC CGCGAGAAAATGAAGAGCGGATGACACGAACTCACTGCAGCCGAGAGCGCGCCTCTCGTCGAAAGCCAACCTCGCT SPE1SIyDntNhO:4 GGACCATCeTtGiAcATpCrAiTmGeCrGC SPE4SIyDntNhOe:t5icprimer CACGCCTGCCCGCCTACCGCACCTCGCGTCGACCGCCGGCCCAGGAGCTCCTCGTAGCGGCCTTCCGATACGCCAGTGCCAGCCGAAATGCGGGTCCTGTTCTAGTGCCAGAGGTCGTCCAGGCCCGAGAGCCTG GCGCCTCGCTCGTCCCCGTCTTTTCCTTTGGCGAGAACGACGTGCGTCCCCTCTCTC CATCCGCACCG AGATCGTCTCTCTGTGCGGCGTGCTGACCTCGTCGACGTGCGCGCAGATCTT TCTTGTAGCTGCCCTG AGGGACGCGCTTGTACAAGCTGCAGAAGCGGTTTCAGGCCGTCTTTG CAACCAGCTGTCGAACGAGCG CTCGCTCTCTCGCTACGACCCATCGAGTGAATCTGACGCTCG GCTTCACTTTGCGTGCGTCCTTGTCT CGGCCTGTTCAACTGTGCGTCGCTCGCCCTCGTCGAT GCGACGTGCGCGCAGCCATCTTCTTCGGCCG TCCACGCTCGCAGATAACATGGGCTTGATGCC TCCTGCTCTCGACCGGCGCACTGACCCTCTCCTGCT CCTTCCTGCGCCGGCGCGCGAGAGAC TTACCGACACCCAATCGTCTCTGTCGGTGCGTCCACCTCTT TCCCTCTTGCAGTTGGCCGTC GGTCGAGCCTCCTCCTCGCTCAGGAGCTGACGTGCGCTCGGCCCACC GCAGGAGCGCTACATC CGATCAAGGTCAAGCAGAAGGACCACCCCTCGACTGCCGACCTCGAGGAGGT TCGGCGCTGAC GCAGAGCTCAAGAGGTCCGTCCCCATACTCGAGCTCTCCCCCCTCGCCTCGCAGACC ACCAAGGAGCTGCCACCTCCAGTTCCAGTCTGGCCTGCTGGTACCGCAGGATCTGGGAGGACTACAAGGAGGTGTACGCCAAGAGCCGC SPEL42I7DNO:9 TGAGTTITnTtC1GBTTKanR5ColE1plasmid CCGGGTC CCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCCAATCCGCCCTCACTACAA CA TCAATTCTTCTAATACCTGGAATGCTGTTTTCCCGGGGATCGCAGTGGTGAGTAACCATGCATCAT ATGCGTAGGTTAAACCGAGTACTAATATAGAGTCGACATCTGGCATTAGCGCTTCTGTGGACACGAATGGGTCTATTCAAAGAATATACCCAGATCCTACGTCGCGACGGTCTATTACGGTGCGTCGACCATCTC AATCGATAGATTGTCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATACCCATA TTCCCATAC TGTTGGAATTTAATCGCGGCCTGGAGCAAGACGTTTCCCGTTGAATATGGCTCA TAAATCAGCATCCA GTTTATGTAAGCAGACAGTTTTATTGTTCATGATGATATATTTTTATCT TAACACCCCTTGTATTACT TGAGACACAACGTGGCTTTGTTGAATAAATCGAACTTTTGCTGA TGTGCAATGTAACATCAGAGATTT TCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACC GTTGAAGGATCAGAGGATCATGACCAAAA TTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAA CCGTAGAAAAGATCAAAGGATCTTCTTGAGATCC AAGAGCTACCAACTCTTTTTCCGAAGGT AAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATC GTAGCCGTAGTTAGGCCACCACT AACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTTCTTCTAGT CCAGTGGCTGCTGCCAGT TCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTA CGCAGCGGTCGGG GGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGG ATACCTAC CTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAG GGC AGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGC GGTATGTGCGGTCCCGAGCACATCCATGGGAACGTATGGCAGGCCAGCTGCAGGAGTGTATGTCTTGTTCGCAATGGGCGTGCGGATACAACGGGCGCGTGGGGCTGAGTACGTCTCTTAATTAGGGTACCTGTCG CAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTT AAAACGC CCTGATTCTGTGGATAACCGTGGAGTAGGGATAACAGGGTAATGGACCATCTGAA TCCTGCGTTATCC CCTACTCTGGCGTCGATGAGGGAGTAGACTTCTTAATTAAGACGTCAGAA TCATGCGCCACATGAGAC TCTCCCTATAGTGAGTCGTATTAATTTCGCGGGCGGAACCCCTAT TTCTCGAGGCGGCCGCATGTGAG ATGTATCCGCTCATGAGTAGCACCAGGCGTTTAAGGGCAC TTGTTTATTTTTCTAAATACATTCAAAT TGCCACTCATCGCAGTACTGTTGTAATTCATTAAG CAATAACTGCCTTAAAAAAATTACGCCCCGCCC GAACCTGAATCGCCAGCGGCATCAGCACCT CATTCTGCCGACATGGAAGCCATCACAAACGGCATGAT GAAGAAGTTGTCCATATTGGCCACG TGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGC AACATATTCTCAATAAACC TTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACAAAA TGTGTAGAAACTGC CTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATA AACGGTGTA CGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCTCATGGAA TGAG ACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGCCATACGAAATTCCGGA TTAACAAATATGCGACTCCGATGAGACTGAGTGCCCAAAGGCATAGTAGATCGGAGATTCATAGAGGTGTCACTGAGGAGTTAAACAAATCTTGTAGGTCGACATCTTAGTATCTTTGTACATATTTGACCGGTCT ATGTTCTTTACGATGCCATTGGGATATATCAACGGTGGTATATCCAGTGATTTTTTTCTCCA CTCAAA TTAGCTCCTGAAAATCTCGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCA TTTTAGCTTCC AACCTCTTACGTGCCGATCAAAGTCTCATTTTCGCCAAAAGTTGTCATGACCAAAATTCTCACTTGTGATAGCAGAAGTTGG SIE Gnt1IBDKNaOn:R510ColE1genefragmentflankedwithBsaIsi GGATGCTTACCAGAGTATTCATATACATTAGACTTATCGCATTGGGGATACTGGGCATAGGTATGTGTCCACTCAGAGAGTGTACTCCGGTCCAAGGTCGCGt ATe GGs TATGTTAAGATCCCATGCATCATCAG TGTAACATCATTGGCAACGCTACCTTTGCCATGTTTCAGAAACAACTCTGGCGCA TGACCATCTCATC CGATAGATTGTCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATA TCGGGCTTCCCATACAAT TGGAATTTAATCGCGGCCTGGAGCAAGACGTTTCCCGTTGAATAT CCCATATAAATCAGCATCCATGT TATGTAAGCAGACAGTTTTATTGTTCATGATGATATATTT GGCTCATAACACCCCTTGTATTACTGTT GACACAACGTGGCTTTGTTGAATAAATCGAACTTT TTATCTTGTGCAATGTAACATCAGAGATTTTGA CTTAACGTGAGTTTTCGTTCCACTGAGCGT TGCTGAGTTGAAGGATCAGAGGATCATGACCAAAATCC TTTCTGCGCGTAATCTGCTGCTTGC CAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTT AGCTACCAACTCTTTTTCCG AAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAG GCCGTAGTTAGGCCA AAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTTCTTCTAGTGTA GTGGCTGCTG CCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCA AGCGGTCGGGCCCTAGGATAGCGGCGGGAGTGAGATGTTCCGGTTGGCTACCTATCAACGCCGCGCGATGTCGTGTAGCGTACGACAGGAAACCGGAATCACGTTATCAACCCCGGGAAATCATAGGAGGCAGTCA CACGTGAGCTACGGCGGATAGCAAGGCGTAAGTAGGACGGACAAACGGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGC TTCGCCACCTCTGACTTGAGCGTCAGGAGTGTATGTCTTGTTCGCAATGGGCGTGCGGATACAACGGGCGCGTGGTATCTTTATAGTCCTGTCGGGT CAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCAGCGACTGGGTATGCCTCTTTACTCGTGGACAGATATAACTGCCCCCACG GATTCTGTGGATAACCGTGGAGTAGGGATAACAGGGTAATGGACCATCTGAATCATGCGCCACATGAGACCT SOE CLTIAGI COD T3C0N T5O: GGCCh1 Gl1 ToCrGRATTGwAiGsGtG3AGFTWADGACTTCTTAATTAAGACGTCA SOELIGIOD30N6O:Ch1l2 CGGTTGTAGTGAoGrGRGCTGwGiAsTtT5GTRTECVGAATTCGGATCCCTCGAGC SIEnt1IADKNaOn:13 CGGTCTCACRC3GCgGeGnAeTfragment,flankedbyBsaIsites CAATTAACCAATTCTGGAATCTAACGGAAAAACATACCATCCGAATCCTGAAAGCCTAATTCAAACGGTCCTAAGGTAGCGAACCATGTGTTACAAC CAATACCATATTTTTGAAAAAGCCGTTTCTGTAATGAAGGAAAGTAGAAAAAACCTTCGACCACAGTATGTGACTATGCTATTCACTACTAGGATTAT AAGATCCTGGTATCGGTCTGCGATTCCGACTCGTCCAACA AGGATGGC ATAAGGTTATCAAGTG TCAATACAACCTATTAATTTCCCCTCGTCAAAA CTTTCCAGACTTGTTCAAGAACAAAGTGCCACCACGACTCGAATGTTAGCAGCCGTACCGTTGCAATCCGGTGAGAATGGCAAAAGCTTATGCATTT CATTCGTGATTGCGCCTGAGCGAGGCGAAATACGCGATCGACTTCGATATAAAATACAAGCGTACCGACAATTTCAACAACACAACAAACCGTTATT TGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATATTCTGGAGGAAACTCCGGAA SIE Cnt9IDNaNtOR:L14g GGCGTTCCGTTCCACGCCCTCATGe CCn AGe AAGCf AGr CAa GCg GGm GTe CGn ATt TG, CGGGf TGl GCa CTn AAk CCe CCd CGGCb CTy CCGGB ACs TTa CCI GGGAs CGiCtCeGsACGCGGTGCTGCATCGCGTCGATCGC GCGCCCGAGGACGGCTTGG GGCAGCGCGTCGGCGCCGGCGAGCCCGACG AGCTCGCGACGGCGCAGAACGGCTTCGGCGTCTGCCTACGTGTGCCTGGAGCCGGACCAGAGGCCGCGGGCGGGCGGCGTCCAGGTCAACACTCAGC CCCTGTGTCGAGCGCAGTGACTGACTGTGGCTGTCACACGGGCTCGCCTGGGCTAGGCCGGTCCACACGTGCTTGCTGGTGTTCGCGTGCATCCGGGT CACCGAGACGCTCGCGAACGGCAAGGAGGTCAAGATCTGGGCG CACAG ATCTGAGCCGTCGTCGTCG CGGCGAGTGTGGACGCTCGAGCTGAGCCTG CTTTTCCCTCGCTCGTCTTTGCTGTTTCCGCTGTTGATGCCGTATGGGGTTGCCCAGGGGCCTGCGTCGTGCAGATTCCCCGGTCGCGATACCCCCC TTCGAGTGCGTCCAGCGAGGGCGAGAGAGAGACGGTCGACACGCCTGTCCCTGTCGCTGAGCTAGTTACCGCACGGGTTCTGCTTACTGCACAGCAG CGCGACGAGAGCGAGGCGCTCCTCCTCCCCCCTCGCCCCATCT CTTGGC TGTGAGTACTCGAGGCTGC TCCACCTCGCCCCTCTCCCTCTAGTCTTCT TGGCGGCCGCCACTCTTGATCCGTAACCAGCCGCGACATGTCATCACGGAGCTCACCCCGGACCATCGACCCGTCCACCCACTCCCGCAAGCCACGA GGCACTGGATGGGTCCTTCACCACCGACACCGTCTTCCGCGTCCAACGCTGGCTCCACCCCGGGGGGGGGAACCGGGCCCTGTACGAGCCCCATCGA GAGGTGCCGGTGGACCCGCCCCTGACCAAGGTGTTCCCCGAC CTGCGG AGGACGGCGACCCGGACT GACGAATCGGACGACGAATCGGACGCCGGGG CTCGTACTCCGGCTGGAACCCCCGGCGCAGCGGCTTTGCAGCTCCGGTCCGGTAAGCGGAGCGAGTACCGACGGCGACCTGGCGGGCTTCGTGGTCGT GTCGGGCGCGCGTTGATGGGGCTCGCGACGGAGTTCGCCCGCGGAAGGCGGTGCGGGCCCGCCCCGGGGAGGCCAACCCCTGCGTGGGGGCCACGGG TCACCAACGTTAACGCACCGGCTATCCACGCCCGCTGAGACCG TGGAGG SIE CnGtG2ID TCNTaN CtO AR: CAR15 CAgTeGnAeCCfArAaGgGmTeGnTtT,CCfClCaGnAkCeGdACbGyAABTsCaGIGAsCiGtAeCs CCCGGACTCCCGGACGTTCGTCG GAATCGGACGCCGGGGAGGACGGCGA GGCTGGAACCGCCGGCTGACCGTCCGGTAAGCGGAGCGAGTACCGGAAGCGGTGCCGGCACCCCCTGGGGACGGGGCTTCGTGGTCGTCTCGTACTCC CGTTGATGGGGCTCGCGACGGAGTTCGCCCGCGAGCGGGGCGCCGGGCCAACCCCTGCGTGGGGGCCTAGCGGAGGGGGTTCCAGCGCGACAGCCGG TAACGCACCGGCTATCCACGCGTACCGGCGGATGGGGTTCACCCTCTG T GGCACCGCCTCGGACGGCGAGCAG CGGCCTGGACACCGCCCTGTACGAC TCCAACCTCGTCGTCGTCGTGTCCGCCCGCCTTCCCTCACCGATTCGCAGGTCTATTGGCCCCCCCTTGTCCCCCTAAGCTTATTCACCTGCACTCG GGCCCCCTCGAGCGGTTGCGGCCCTTACCCCCCACCCACACTACTTCTGGTACCTGTTTTTCGTTTCTGCTGCTGCCACCCGGTCTCCCTGCCCCGCT PGL CC0 GT9 AC1 TTGT3 ACx CA- AAF ATL GGA GGG GA- CCG TTF CAP GCGAg TAe GGn TGe CAGCf AGr AAa GCg GGm GAe CCn GGt AA, GCGAf AAl GGa CGn TAk CCe TTd TATCb AAy CACAS GGa GAp CCI GGTAs CTi GGt TAe CCs CGCACAAAGACTATAAAGACGA GGCGACGTCAACGGCCACAAGTTCTCGGTTTCGGGCGAG GATCCTCGTCGAGTTGGAC TCAAGTTCATCTGCACCACCGGCA GGCGAGGGAGATGCCACCTACGGCAAGCTCACCC CCAGTGCTT AGTTGCCGGTCCCGTGGCCGACGCTCGTCACCACCCTCACCTACGGAGT GTCCAGGAGCCTGCCGACCGCCATTACCTCTCCGTGTACCACAAGCGAATTGGAAACGGCGACGACAACCTGAACCATATGCATCTCTCAGACGGTCGGCCATGCCGGAGGGCTAC ACACCCTCGTCAACCGCATCGAGCTCAAGGGCATCGA CCGAGGTCAAGTTTGAGGGCG CGAGTACAACTACAACTCGCAC CTTCAAGGAGGACGGCAACATCCTCGGCCACAAACT AAGATCCGCCACAACATCGAGGAAACCGGGTCCTTCAGCGATTCCCAATGGCGTCCGGGCACCGAAACGCCAACGTAAACGCAAAGCCGAGGCAAATCCAACACGCGCTCAACTTC ATGGCCCCGTCCTCTTGCCGGACAACCACTACCTCTCGACCCAGTCGGCC GATCGGAG GCGCGACCACATGGTCCTCCTCGAATTCGTCACCG CTCTCGAAGGACCCGAACGAGAA TAGTGAAGAGC CCGCCGGCATCACCCTCGGCATGGACGAGCTCTACAAG SRE IDNO:26 GCtTaiwanensisRPS3Apromotergenefragment,flankedbySapIsites CTTCATGTGCGATCCGGACCGGACGTCAAGCCCAGGTCGTACCGCTAGTGGCCGGCTCAAGTAAGACACATGACGGGTGGGCCGGATGGTCACACGACCCGACTCGGCAGCAGAGC TGTGCTGCTGGACGCAAGAAGGCTGATGTTG CGGGACAATGTCGGTCGTGCATTGACG GGGCGTGTGCACCAGG GACCGTCGAGGCGTCAGGCGCTGTGGGCGGGGTAAGGTGCTA CTATCGTGTGTGTTCAGCACGAAGGAGAGGCAGCGACGGCAAGCCGGTCTGAGCAAGGGCGGGTAAGGCAGGGGTGGAGTCAGCGGCGTTGGTAGGAGGACACAAAGTCAAGCAAG GCGGGTGCAGAGTCGAGGCCGGCGTCGCCGACACGCGGACGAGC GGCGCGCGCAAAAA ACCTCGCTCTTGTCCCTCGCACCCTCGCCG GACCGACCGACTTGGTGTCGAGCGCGGCA ATCCTATACTATCGTCGCAGTCGACCCTCCGCCGCTCCTTCTCCAACCCGCCTTACGGGCCCCCCTTTCAGCCCACCAGAACCAGTCGGGGGCCGAGATGGTTCCAGTGTGCATGCG CGCTCCTGGCACGGCCATCTCCGGCACGTCGTAGCTCGGCGCCCCACGTTACCGAACCTCCCGGACTTGCAGGCGAGAGTGTATTTCGCCCGCCGACTCGACCCCGCCCGCTTCG CCTGGGTGGGCGGGAAGGTTGGGTCGGC TTAGAGTGTACTGGCGGTATCGTGCACGCG GCCGTTTTCAGTC GGGTCGGCTAGGTCGAGCTCGGCAGGCACGGGTCGGCGGTCACGC CCGCGCAGCGGGTGCCATGCGGCAGATGCGGGCCCTAGGCCATGCGGGATGACCGCGGTCACCAAGCGGCCTGCTGCGGACTCCCTTGCTCCGTACCGCTCATGACACGGATGGCGG GTGCATCGAAATCGCGGGGAACCTGGCGCTAACCCGGCCTCTGCTCCTGTCCTACAGCCATGACTAGATAGCACATGAACGCCCTC SPE GLC0T2I C4D TTRN CPO AS: T3AA27 GGtCeGrGmAiGnCaAtGoCrGAgCeGnGeACfragment,flankedbySapIsites TGCGAGGGAAACT GGACCTTGTGCGTTGTGTTTGTAGGGAGGGCGAGTGGACCCGCAA GGTTGGTCTGCCGCGTCTTTGCCTTCCTGTCCGCCTCTCCGGTTCGGCTGTTGCGCGTCGTCCCGCCGTACGGACGTAGCCTTTTGCCGGGACGTTGCCGAAGTTGACGAGGAGAG TCGATGTTGAGTGTACTGCTACATCCCACGAAGAAGGGAAG TTCTCGACGTGCTCTAG GACCGCATCGCTGGCCATCCCTCTCC CTCGCACGGCCGTGAGACTGCTCTCTTCCCTC AACAATTGATGCTGCCGCCTACGTCGAACGGCCGTCTAGACGCCGGCATCTCCCGTACCATCGACTTGTACTTTCGACAGCAGGTCGGCAAGCAAGATTTTCCTGCCGTCGGCTTG CCCCAGTCCCGCCGTCGACAACGCCGCACGCATGTTGAGATCTAACGCAATTAC TTCT AAATGAAGAGC ACCTATACGATCCTTGAAT SIE CnGtG3I T4D C5T6N C7O A8: AGS2 Ca8 GpCIGAdTrGoApAoGuAtGCgTeGnGefragment,flankedbySapIsites TGAACATTTTG TAGAGCCACAAACAGCCGAAAGTGAAACGTGATTTCATGCGTCATTT CGCGGCAACTCTAAAAGAATACATCTGAGTCTATGAGATTTACAGTGGATTGCTTGTCAGGGCCTAAACTTTACGAACGAATATATGAAAGTGTATGAATGAATGTTTTCTTAACAT GCGAGGAGCTGTTCACTGGTGTCGTCCCTATTCTGGTGGA AATACTAGATGCGTAAAG CGTGCGTGGCGAGGGTGAAGGTGAC ACTGGATGGTGATGTCAACGGTCATAAGTTTTC CTGCCGGTTCCTTGGCCGACTCTGGGTCAAAACCGTAACAGTCGTGGTAACATATCATTGGAGCTGGCTTTGCAAAGGTTGTCCTATTTCGTCGTTCAGCTTTAACTTCGCGTAAA ATATGAAGCAGCATGACTTCTTCAAGTCCGCCATGCCGGAAGGCTATGTGCAG GGACC GGATGACGGCACGTACAAAACGCGTGCGGAAGTGAAAT GAACGCACGATTTCCTTTAA AAAGGCATTGACTTTAAAGAGGA TTGAAGGCGATACCCTGGTAAACCGCATTGAGCTG TTTACATCA CGGCAATATCCTGGGCCATAAGCTGGAATACAATTTTAACAGCCACAATG CAGCGTGCACGCCGTCGCGGCATTGAAATACCAACATAAACACAAAGTCGAGACAAATCTAACATACGCCAGAATACTGTGTTTGAAATAGAGTTTCGCCACAACGTGGAGGATGG CACTATCTGAGCACGCAAAGCGTTCTGTCTAAAGATC CCTGTTCTGCTGCCAGACAAT TCGTAACCGCAGCGGGCATCAC CGAACGAGAAACGCGATCATATGGTTCTGCTGGAGT GCTCAGTCGAAAGACTGGGCCTGTCTACTGGTGTTTATTAGTGCATTGGTATAGCTTTGTTGATCCAGAGATTGGAAACCCGACGTGCCTACTTCAACATAATGAAAGAACGAAAG GCTCACCTTCGGGTGGGCCTTTCTGCGTTTATACCTGCAGGGGTACAAGC TCACACTG AGTGAATAAAGCTCCACACAGTCGGCTATGAGACCG AACGATCTCCAGCTCTTCAAAAA ACCGCGTAAGCGGGGAGTCCAGTGCTTCTCGCGCTACCCGGACCACATGAAGCAGCACGACTTCTTTAAGTCGGCCATGC GTTTGAGCGTGACCGGATCCACCAGGAGCGCACCATCTTCTTCAAGGATGACGGCAACTACAAGACCCGCGCCGAGGTCAA GGCCACAAACTCGAGCTCATCCAGATCCTAACCGCATCGAGCTCAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTC AGGTCAACTTCAAGATCCGCCAACCAAAACCATTCCGGCACAACGTCTACATCATGGCGGACAAGCAGAAGAACGGCATCA CCCGATCGGAGATGGCCCCGTCCTCTTGCCAGGGGAACCAGAGCCTCGGTCCAGCTCGCCGACCACTACCAGCAGAACAC CCGAACGAGAAGCGCGACCACATGGTCCTCCTCGAATCTACCGTTACCACCTCCTCGACCCAGTCGGCCCTCTCGAAGGAC AGCTCTACAAGTAGGCGGAGCAGCGACGGACGGACCTTGTGCGTTGGCTCGGTCTCTGGGCATCACCCTCGGCATGGACG CAATGCGAGGGAAACTCTTTCTCTTCCTTCGTGCGTCCTGCCCGAGAGACTTTGACGGGAGGATGCGGGCGAGTGGACCCG GAGGGTTGGTCTGCCGGCTGCTCGCGCCCGTCGTTGGGCTCGCTCGCTGCTTCGGCTGCTATACGTTCTGGAACCGAGGA TAGTCGATGTTGAGTGTACTGCTACATCCCACGA GTGCTC CT AGAAGGGAAGCTCGCACGGCCGTGAGACTGCTCTCTTCC TTCGGAAACCCAGACTATCGCTGGCCATCCCTCTCCACGCTTGCCGCTTCGACTGCTTCTCAACGTGCACAATTCGCTGC TCTCCCCAGTTGCACTCGGCCTCGGCCGCCTACGTCGAGCGCAAGCGACCCTCACATGATTGCGAGCGAGAGTTCTCGCGT AATAAAAAGTGAATAAATGCCGTACCCAAACCGCCGCACGCATGTTGAGATCTAACGCAATTACACCTATACGATCCTTG CGGTGCTGCATCGCGTCGATCGCGACCTACGGTTCCGCGCCTAGCGACGACGTGTGGGGCTACCGCTCGCTCGAGCCGACG CGTCGGCGCCGGCGAGCCCGACGGCGCCCGAGCGCATCCGAGACGTATCGGGCATCGTGCACCCGCCGATCGGCGGCAGCG CGGCGTCCAGGTCAACACTCAGCAGCTCGCGACGGCGCAGGAGACGGCTTCGGCGTCGCAGGGCGACGACGGCGGGGCGGG CGTCCCTCTCGTTCCTCTCGGGTCCCTGTGTCGAGCGCAGTGACTGACTTCGTTCGTGTCCTTGGCGCAAGCCTGCGGTG CGCAAGGTGTGGTGGGACCACAGCACCGAGACGCTCGCGAACGGCAAGGAGGTCAGATGCAATCCATCGGGGGCCCTGCAG TGTGGACGCTCGAGCTGAGCCTGATCTGAGCCGTCGTCGTCGTCGTCGTTGTCGAGGTGCAGGGCCGGGCCGGGTCGGAG ATTCCCCGGTCGCGATACCCCCCCTTTTCCCTCGCTC CAG TACAT GTCTTGTTTCCGTAGCTTGGTCCGGCTCTCTTCTTG GGTGTACCGCACGGGTTCTGTATCCAGCAGTTCGAGTGCGTCCAGCGAGGGCGAGAGAGAGACGGTCGACACGCGCCGCC CGCCCCTCTCCCCTTCCTGAAGCTTCTTGGCCGCGACGAGAGCGAGGCGCTCCTCCTCCCCCCTCGCCCCATCTTCCACCT CCACCCACTCCCGCAAGCCATCCGTATTGGTGGCAGGTACTCGAGGCTGCTCTACGCCAAGCTAGACCCCGACTGACCCGT CCGGGGGACGCCGAGGCCATCGAGGCACGTCGCGGACTCGAGCGTCTTGACGACACGGCTTACCGGTACCGCACCAGTGTC CCGGGGACGGCTTCACCCTGCGGGAGGTGCCGGTGGTACCCCTCTGCCACCCACCGACACCGTCTTCCGCGTCACCGCCA GGACGACGAATCGGACGCCGGGGAGGACGGCGACCCGGACTCCCCCGTGGAACCGCTATAGGTGTTCCCCGACGACGAATC GACCTGGCGGGCTTCGTGGTCGTCTCGTACTCCGGCTGGAACCGCCGGCTGCAGCTCCGGTCCGGTACGGGGACGACGGC CCCCGGAGCACCGGGGGCACGGGGTCGGGCGCGCGTTGATGGGGCTCGCGACGGAGTTACGGGCACCCAGTCCGGAGGTCG CGCCGGGCACCTCTGGCTGGAGGTCACCAACGTTAACGCACCGGCTATCCACGC AGCGGGG SOE IDNO:31 ALCICGTOC4A9C6CTCGACCCTGTACGC SOE IDNO:32 CLGIGGGOC4G9A7GAGGAAGGAAGGTCA SOEL IDNO:33 TCITGTOC5G0G2CTACCACCCTCACGG SOELIGIDNO:34 ACGCOC5G0C3ACAGAGAGACGATCT SOE GLAITGI GOD T5A0N G0O G,: GGs3 Gy5 CnCtGhTeCtTiCcAGoClTigonucleotide SOELIGIOD51N4O,:s3y6ntheticoligonucleotide CCTGCACCTCGACAACGACGAC SOE TLCITGI TOD C5G0N G2O C,: TAs3 Cy7 CnAtChCeCtTiCcACoGlGigonucleotide SOE ALCIGGI COD C5G0N C3O A,: CAs3 Gy8 AnGtAhGeAtCiGcAToClTigonucleotide SOELIGIODNO:39 ACTCG5T1C5C,AAsCyCnTtChGeTtCiGcTCoGlTigonucleotide SOE IDN ALGIAGCOC5T0C5O G,: ACs4 Cy0 TnTtGhTeCtCiGcAGoClCigonucleotide SEE MSKTF1ID LCfLrN HoO Gm: AYA4u1reobasidiummelanogenum VEGIRVFPEAGENTIPPEADFARLVRALLGMPPMRIDDDAMLEEIFGDFGASDAASRFGELFAILEGRLVYSEVAVLPDPAPDGPFEESYFGPAPHYRFLKDRGEAEASA RMRSEGYVPRIKAAIFEFLMVGSWAPVAKLDTLAIEANDVVPPAELDS ISGIIGYSEGASAAATLVYDEE SAGGHTIPRHGKLL NDSEAVDELNLLALPEAVVPTSGLKHRILVDGSAANVDDPIYPKNDLGSAFLLAKLNYENDIAFDDNMAVFFD S0E4-8IDNO: ALSR7 NK7 DAGRP FVu ELt DCa4 PLt2 MLN RHi EGv VFe RA E PLNs SSt LRe VVr RLa TGs VAe LKELTAGAPEFRDIGFVDWGGHFVSELGVAYAVTDAAAPINLICLALLKVPATRMPAWYLDHNPSAPFDSESPTYPASPPKGDVEAPWRPSPWAWPH KFAVFCSGYLPLDRRCESWFDSPVNTPALHVLGRSDVVPARPTNSESRSTPLFAPNAVEPDRPFLSMNRS F MFKDFILSKTFPVEPPLFPLFAPSSGVSRLASPFDS SRPVVETWVHMEPGLGSHPYAILPHRKPHFAH SPE MrDoItI AeD LiDnNO FFI: DDE:43 YV2G3D5K3L,YSpYuLtDaNtPiLvAeKFfAattyacidhydroxylase SLPRDNMLRAISLYGITYVGIFVLYFSPVALTGALSSYAYSLLIAFNDAKSRSMSESPHSPFRAFSLLKDNLSVSAAKEAIAAAFSSSLVEAAAFYPLMALADVLPLGLS WFVGDVRGYSLYDSIAEGPFGDKGGVLPWLYMAFSAALFLWFTDFAIYWVHR TLP PTPFASHAFHPVDGYFSVPYHMACYMFPIHKYMFI WLHLPFLYKRLHKPHHKWII HLYFTCNYGYFTWADKAF GLFSFVNLWSIFIHDSDMLCGHPLEHYINGPAHHTLH D SSFRVPAKDDDPLVAILSGRTNNHATVSAPAPLATGPAPAKLDIATPSPSPTLA RAPPRSRAELGLLRRTAARAKAVVAPEMKRVDSGLGSETELGLAGSARSSGASSSSASSSGDEGASEKKKAVPAAAATGAAA SPE MrotIeDinNOI:D:442354,puta VSTIIASELSNDIDPVSFTKLLFADDLGIKKIENGGLEt KGi AMv FSe MESKe GEs KKt LKe KDr VNa RIs GKe NKIVMNLGAITFKELMDNTVVKLSKGGSANEKAKTAYNTLIDLKKEGKVYKGPAKPKAD SPE MrSoFtI DeD DiLnNO AI:DP:45 AD5P1A4V3L,ARpSuLtLaDtKiIvSeSPmAaSnGnDiDtEoLlPdehydrogenase PAVILPMDGFHRTAELAADPDPELSFRRRGAPFTPFRARPYDLKVLALLDALGVIRPRGLSRGTKDSETRFLSTAAKPLALFDSHHLANDSKPDSPSVSEDGPASISAPI ERPHHCHVRAIHVMVLVREPGDNRYLLLDEPVWTDVSREMDERWFYRVPEDVALRRIIKRHVAGLADEAAEAKALENDVLNG EAIAEAGGDVAIIILGERERINDHDTALKPASEFELGRASSSPSDGDFPRPTPLSDSVMDLFSMKGRVSAITGGGSGIGWATA SIDENYALDSWKTMDVNLNSTFWLCSAKRRAFCNAIKRWCFKKAKYACDATDAEAIEKTIDAVGNDFGRLDCFVANAGGGVPG HFCRSIARDWRNFARVNCISPGFFDTAMGPSDAEVEAKEVSVGEVRKLASSVFFIGARTTSISARIVNVPYDPAYNSSKAGVV ILVDGGYCLT PGNVKELKAAYLYLASNASSYTTGSD SPE MrPoStI ReD RiPnNO PPI: PDP:46 LD5H1P5S2L,AApNuYtRaCtGiSvTeGSgPlAyAcSoLsAySlTStVransferase EPNGFT GPAPLDASKGRFFLDSYGRRLLLHGANVSGLDKLPT ALVSLFHPLDYMGGIDRACYYFVDDGAAHSISFVGRPWPLEESHEHLSRLRNWGLTFIRLVVTWEALEHSGPGEHDAYIAYLH TKLAAATAATVFWGGDVFADPVKWRSRRVHRARGRGLSHGAPLWTLSLVGFDVRNMKATGAAHAHNLHLEPHDPPPNVWPSGV EVMNEPHKGYIELLSPYAWDFTADLAIGYKFGPESWAGVGSGWGADLDGESEGVGLTFLESMCEAFGVLADRLRDLEGVMGF WLSPSSPAFDALPTSTTGCLWAEHGVWWDARGEVGEGVVLHKSVELYVFPRHRYFAPPASDFVPVVLTEAVTHHVLLVPPRSV EGEEVSWYRDFYFPFVRKFSARIRRAPNPPTWFTFVEPMPNEFCPTYPTVSRPRGMGICYVAEPMHEWGYGDELGGTRLKGRR LGFMTANVGLSRGMFLLKALYFGRKGLKKNYAIISTI FEKK FWERMLDGIC LRHAYRLGETPIVLGETGVPFDLNKAAFSTKD ARALDAVRPYASCAKITGAEGAIGPLLSRNTFSNFLWNYNALNNDEWGDSWNGENFSWFSSDVTPEALKAAEDGGEAARLNVG TEVFLPARRYGEAARSGRLRVLRDDLGHDTGRERWFRHYLDSEYELLNPTIPPSHPFAAAVPAVADAEPDAPPLVGAECRARE PAALLDALALDAVWVHLVLVVGIGGYMGWWLLGVWRGLEYGVILAHTGNWTGTAPWGGFGVSHGSPLVTPVSTFVELEGLPSDRPSPRAWYEP SPE MrPoStI ReD PiVnNO TVI:D:475149,putativeCholineCarnitineo-acyltransferase LHHRLKEYAASATGPRIANSSYFIPEAEGWKWTTFGGLLPKLPVPPLEDTLARYLKALEALSPAEHERTKKAVKDFEHEGPE LEPDVRGTPLDMSYKLFEGSTYALRSIHPSTERSTVGVCLESLLRNIPFFILEDDPTPARGNLMRATSLILASLSFIHDLRTG LTAIVADAGRTPPNVASALGVLSTERRATWASCRDASGELSMRKHNIEVGVNLSCMRCGLFYWFEVLDSKHRPALTERALLSN NNMLCGTYKLEKGVVGTCTNRWYDKLIIVAANGAAGVNFEHSGVDGHDTVVILDRKYAVLAFDVVVYATLEDDTSPETASEMC AAGLFKAKLSPWAKGGPGKKSAPADAVKDGEPEEIDVAPKKLEWIMTPELKMAVRFAETRLLSIDLLRIFCARNSEIANVPAA EFDVYGKNAITHGFSPDAFVMAYAAYFSLYGRTECVYEPA L ASPREKIDALRK MTKAFLHGRTEAVRSVTPESVAFVKTFCSE SVKIAERIPELFAKCDKPAGHYTADLLTGRHSCTSLKSGTLSGDRILYAMYCLAAREKRRALSNGDASSSSSETESSDEADEV LDALAYFVEVHRLLKLHEATRKPNSNRCFGVNDVHSFLARGLEFIGDFAGKPTVGVGDGLGIGYIIKEDSISVVASSKHRTRY DVEKALSDRHGAAAKEGGTAAAKRRGIVPGTRIRTVEL PITHLHADTRRAEDELSYSDGYGFYGALT ensae , a eerences sn.asess: omcero oeaacenoaucsoreeass.oamrreonwceanrao.cocma,aocmo enscocea maorrac cero- orae ,ne,eseman ,o,onor,cees., es a.unnc- non- ,a - meaosmne oeanouseas oosorumoruoes.oma eeonr.o emces. o oarn : e uonowe,szue,r. aso: n a,. cacroauannne asno,e. ,ru cenoncmo,nreaaeonesno,vmeeceeswnoamne-,scaaea moe,oraoo,osaoor,um s:,mocr:oa.ceac.moerc. .e , an eno caa,ean ommun rara,us,rnau es.eoum,eocmenra.comarces. s - - - av oc, an ra oun-assaa,rnacar, veren, ruceerman, caocooeorruc,earos. an:auxr–eancae.”u.aorurnosa:o o. “ o.nsoreumrssur oaane .aocurs socoroosuc aonno ooonoerrcaucnaeouoaareva,e n aon. ara ,eu,aa,u,e ,erman, e a.-xrac-eua-r.unaoo s: neow: cass ooena vaues.oecnoo vances. :–. eon..oecav... us.eer,ss wa:coar.eo,nrearaur.zaeuaenaeroc,o aanne.”auscoenccos. “esearc:nve, non.recemunear,ene: e–raan.nsocor:o.e,vaensrm o c,aroamenoooen,coercneesu. n,ouoaosru,a muecssaan,o esa a..crooeone c.user an:–ours:,wueev,er,c. ouce.non, oa amromaec c,emesceans,, aanureeonmm,unecwarnons car,onr mceea noo.smn,eas.nocman,wwa.neawu,re.oconmneaercuesnse,o-a-e,-eaeruca aurnezuaas.e “ouroaocreuacavwanoemnssareoorooourcueasaoeavcaee,aeawre.n”ceoumano,u anns, w nroa.n oeaarna n-r ouesr,nenasez:, e o.o.. oruaero,s ru.:o oem.o serarz,. ..erourna.one. asso,.romosome-eveenome assem annaonmranc,ssc.romzeer—,a.see awnneoear,on. oe oor:a.er,soesr mrsea,-omc e-,nnee-nern- o,arvoeros, ,, – . romo ormmumonsoruo, ees a..crooosee o caocn.suve:. oaos:uea.eno,mmoe,erernn o,oaosnuosronum,oruaoeens. m,eerree.r.:u eexe-. -as- xnoreearnoveer.,resosn ounr.,e anou-aar,oenraonaro,ucaonvene-o.oorouseaoeruaooessm:n asnseoreucu ore ena,naro,naoenoecno. : .m: uar.erovrna.nero,emaaonur,smaeoua,seammev,oeroes, aeaaorcsnraane-aensa, aesnvsaonc.eare-a wanomauveaer.oo “nucenoonmen-caoeooeruaaoocruooeesn.”eveeas s:o.or. ourna aoo , no. r, : e . coeunz,nce.eernnacr,un, neoen.xeauo. e,c nu aesn. eeumonn. naoo. “osevoeroummenor ouo aes.”oecasnoose amnor mceuz,sra,aer, : –.s:o.or. .. osa:o.morcucrraoooaaruceoeaesacoresm,erraovcee,sn an,aranaas, a acnooaroou.ceonaroomc s ennneeecrn o oomon,eer.,cromroens.eom.e.cenarear.comarces. s -- - n.manamenousun.”rensns,c arnoocoar,.ver. “econeanno .occcumaoas nsn: no.une, :– e ane,o. r. “eo aar enea,.ranroxo-s.m eae. eonne oevnre.,. -caoro. ronxseraoasme.”,saceoae aansen arv,nrownmeseenunanoez, amcnraoocoar , ce n oavueon. –.cea “a ..”u,ov ena. rne,em a, an.e ner eoo eosso e omuo: r:as,ornro.– nc oaers. eroo ,nur aoes nre: .os,o c..or s:uacosrroo. .roava roe,so. ., eee.rene,a.- --noenunsanr -eeea,s a.n -amr.rm-ows.,a an,nen,oroeesma-maro,onune,oan, ana _. encnneoeornorncrceoaseer :ccumua.onsn:oarrowaoca –evoe-wu.n”.o “reseouarcoec nan,uan,ere.erer,ares.ue.orr,..orec.. oresneoerner.oaoo.s “onrnuemernoruooesosororncuremaseoruoaeserwooru.nccaroeunar.e”sre,oeacmno.rooruc ann,o ann: nuee,n a-neae,rne,, nou.aneau,: –.s:o.or. . ven.sce-sseo:ruone.oaroree.s.o”snoceesmscaa-owauaorn,aaoe,uaonona,nuur,aa anrnsor,e ann-necreo.n “ oeneamcocns

Claims

m.e c cro na oornm-an: naura occurrnoo roucn mcrooransm, sa non-naura occurrn asm occurrn m acree ora c oesom o ra enr nxesn srmenso: sc roomne o o w au e cenaso e n oone neno - eu nns auoen raeeno oucscurernne mn ccoromorarasnosnmos a neaura aeas one exresseeerooousonuceoe. rve anor .rouece nso onn-nea ourr maore occourron mc sreooerceansrmom acceorronuo co cnasmsn, w o:e aren-er mcrooransm moeromo caron aomsnen esereo a su oxa ac roxa ac moe esereoe ar acoo moe an aceae- non-esere rox rous esereo suaer c aarcooxo m enoe o a a s-uarro axcoao moe comrsn suar acoo moe comr asnn a a moanon eose orr o ar ac moe a - roxa ac moe a aao aaccone es.ereoe carox en o a . e non-naura occurrn mcrooransm o cam, wereneoo s a . .ooe non-naausraro ouccceurrn mec nrooonr-naanusm accorno cam, wereneer o aeas one comarsonoe naura occurrn mcrooraran oscmcurrronm m wccrooreansmsncreasen mcrooransmserve. non-naura occurrn .ooe non-snaurao occurrn, mcrooroansm a,ccornoo cam,, werenoeer, o aeaso one , o , o , o , or o . r.omee no sun-nanuraom occuarrrna. mcrooransm accorno cam, werene mcrooransms r.omee non-nuamurasco omcccuorran or mcarsooromancsoma a.ccorno cam, werene mcrooransms r.omee no onr-nearuraor ooccourarens. mcrooransm accorno cam, werene mcrooransmsr.om ae neonnu-sna seureace ocrcoumrrne mrcoruoor coannsssmn ac oco:rnooo cam, werene mcrooransms orooomces. orua,oosoroous, an a s.ee non-naura occurrn mcrooransm accorno cam, werene mcrooransms ooceosru saeercaeocrvomovaee,rouoo coonrusasnram o:ns,oooooruoaruaaaavuae,enaoooruaoovaa, auena,ooorua saerocara,oosoroous a. c ,ooorua a. oosoroous runenae,oooruaa oosr,oooruaarenenss, oosoroous a. nan. wanenss,ooorua mucuanosa, an a s.rane s neoenc-neaurroam ocecurrorun c moncrsosornan os:m aoccoorornuaoa cam, werene mcrooransms oooooorruuaaaaeevvaaee s srraann --,,oooooruoaaeevvaaee s srraann --,., oooruaae ruaaevae sran -, oooruaraocvaveo svraaen sr -,oooruaoovaa sran - , oooruaauena sranan --.,,oooooorruaauena sran - , ooorua a.auena sran - ,oooruuaa sauaeroecna sran -, ,oooruaarenenss sran - ,oosoroouasr aa s. croaon - - -,oo,sooroous a. coosr - ,oosoroous a. nsran sra snra ooosruoar moucoausn ruosnaen saraen---., n , an o oooruaawanenss sran an. enoe neonno-unsaueranes oc acuerrrenn m ccormoorarasnosnmo acceo erxnres csaomne,v we oerene a enn eoxerensosuosneenve o naura occurrn mcrooransmrom wce non-naura occurrn mcrooransmseernve.e en.oeeno nuosn-neanueras r occurrn mcrooransm accorno cam, weren aromoerore ano eace w aerenromoer, anor weren a’ unransae reon exmr r a’ s ae,erencreasn,ecreasn, or canne reuaon oroesseo enn ooeeno eunsoeenneo.usene ore reuaon oe sa o m asranscre en.oeen noouns-naenueras re occaucrern mcormooransm accorno cam, wereneromoer oe . ooous recomnaon, , znc-ner nucease, or .e non-naura occurrn mcrooransm accorno cam, werene enoenouseene ensouseenouos aenee.en oreroncrease,ecrease, or canee reuaon o exresson o au.xn-en nuocn-neaueraron occurr,n an mc-reoromrnaansumso ancc oor unuo cam, werenee ese e. n, oreoacco ec vruserona e.nese nnoonc-neau orua, s oecnccuerrn, or m recrouoceranns emx areccsosronnevoe c.am, werene enoenous en.oeeno nuosn-neanuerasn oocccuerrn ou m ocrr eooreansmo accorno cam or, werene nucease, or . mooous recomnaon, , znc-ner en.oeeno nuosn-neanueras s oecnccuerrn mcroonrearnesremnc aec,corn soe cam or, werene rozmes, or a -ase meo. ncn, ansense oonuceoes, me.oes no sne-encaeurarom occurarsn a mncroaosran.sm accorno cam, werene -ase e.neea nosn-nnaoucrae o oucc,u srrennce m,c ororo rreaunsm accorno cam, werene enoenous osnecawa cen exressoneve encoes an enzmen aeas aou essorron cuocmonar osornacoec nearoura oc,c wurrenre mnce mcrooransmrouces a non-naura occurrn mcrooransmserve. rooransmrom wc e o.snee nocn-naauwraao orccurorrnuc moncr oooranssm an ac accorrannseor casaem enz,m we.erene enzmene en.zmee nsona-ncauracer oocc aucrrnran msecrraosoer.ansm accorno cam, werene acranserase e.neea nosn-nnaocurea o ouc,c surernnce m,c orro roeruacnesmn accorno cam, werene enoenous osnecawaor caroeno roucon. exressoneve encoes an enzmen a o.snee nocn-naauwraao orc ccaurrorneno mcrorooruacnosnms ac acorunncoon caamcoe,n we cerceansee enzoemneenesnase. a.sen noocne-na ouura, se onccceurr,n or r mecurcoeorann esxmre ascscoornnevo cam, weren enoenousene ecaroxase enzme, a cosneeamnase e encoes an orone-osae oe roenaseeno-o raase enz, ameu, aomoo, a omoo, a- roxac-ransorroen, aeroxsomaa a n ac-o oxase enzme, aeroxsoma eno o raase enzme, a c-o snase enzme, a secree ase enzme, an e roenase enzme, aosneoos roe:a naae roase enzme, a cero--osae roen, or a senransmemra .c cero acranserase enzme, aern-e en.oeeno nuosn-neanuera w o acceurrern ex mrcersosoronanevsem e ancccooresn ano e annz o cams o, werene osaase enzme, a manno--osaee roenaseme, a manno--osae an araoe roenase enzme, aucose enzme, a D-xuonase enzme, osouconoaconase enzme, a-os--osaee roenase enzme, a- osoucosesomerase enzme, aran ouconaee roenase enzme, a ceroase enzme, a saoase enzme, aranseoase enzme, arac- ac aa rox snase enzme, an ace-ranserase enzme, aon-cana- o caroxase enazsem een,z anme, a craeraansseo ernzrmoee,n o,r a aa maa acee snroaseen eanszem enez, amne a.ce- mc.roorea nnons-mna euxraress oecscu arrnee mrocoroooursanosmnu accecoorenao a ennco oe csa amsroeon,a werene seecae marer. roves a ma.reres n aonn- ennazurmae oaccurrorvne msc arnooroancs rmes accorno cam, werene seecae rouces a reure meaocrouc. sance, auorescenroen, or an enzmea mc.roorea nnons-mna cuormars oecscu arrenre m ecxroroerssaonnsm o a acnc eonronenoo auns o camso, werene osnecawa or aeerooousonuceoea encoeense ann aoo roucon oo rouconosnecawa. exresses an enzmen a mc.roorea nnons-mna eura occurrn mcrooransm accorno an o camso, werene sna xresses aeerooousonuceoea encoes arac-ceroase, a ro se, an ace-ranserase, aon-cana-ac aa roxase, a ransor manenno, aea aroce snanse,a ase m,a annn acoe---oos caareoxoasse eanazsem,e a, m ananno c--raeosasaee enzme, aee rrooeennaassee,, a a D--xousoonasuec,o ano araacoonasee, aro-eonsaseo, aucucose--osae osoucosesomerase, aransaoase, aranseoase, or aon maaeaeeeroreonaesnea,s ae enzme. mc.roo mracrnosmas cu acucroer, conmors cnam: one a o cru au croen msoerum owo or more non-naura occurrn rouce e mcrooransm. um an aeas aou oo as no.e m ccurourea m cueuurme. accorno cam, werene mcrooransms secreeeoo mc.rooroannsumce,o come crosnnsr:u acroormoroeru acn aenenocoun aoo roucnos oron o aareeen nuceoe seuenceasomooouso aeas a seue e seuenceneenome oe mcrooransm a nuceoe con romonecre anae ernmconaesor a seroueenncesa arero cvaease a s oeecae marer an aermnaor, werenene mcrooransm. rvnene exresson oe con seuence mc.rooroannsumce,o come crosnnsr:u acroorm eoxerres as nounc oeo aee cerooousenen aoo roucnos a nuceoe con seuen on seuenceor aeerooousene an romoers caae orvnceeane e enxcoreesss aonr ooene coanro sveeuse anc seesecnaee m mcarrooerr,a wnsemre.ne se.ueneceos cnoucoeno oem coznesruocr e axccroerssnonon caemos m orcro,o wraenresmn.e nuceoe con se.ueneceos cnoucoeno oem coznesruocr e axccroersno cam or, werene nuceoe con coon usae oae orae. sonneos mcrooransmn accorance w e e. nuceeooenu ccoeon see counesnrcuec ar aeccoer mnoso c comamm, weren aeas aou oe coonsn mcrooransm. on or secon mos common coonsneos e.ose mocronourceaonsme. consruc accorno cam or, wereneromoersnucen en.zmeeoanruocveoese an conosrcuc res acscaonrcen, aou coaremscen orroe, wn, oerre ann enez smeeecaaer moaurceerss a anreure meaocrouc. se.ueneceoornuceeoeereo coonosursucen aeccourrno an o cam, werene nuceoe con eecon or recover oe exresseroeru ecnc ooese ane aemronooo aucs seeneu.enceaacaes ac.aeesoeneuccoeno ore re ccoonvserruc co amccorrsesn ao cs-aam se,u wenecree cnomer asmnno s axco s neneuencea sne resues, a -a seuence comrsn e amno a consecuve :, or a ca seuence comrsn e amno ac seucenc seeuence :. a.n aoonuoceoero councsnrucoosr r mecraoconra ansmro,m coomer arnsn a: an nuc a’ anor an-ermna omooouso aeas aoron o aareeene seu eoe seuenceas a seuenceromoer an a’ , enceneenome oe mcrooransma. anor aonuceoe seuencea encoes an-ermna n. onuceoe consrucor reacn aromoer an an a’ anor a-ermnaa o amooooouso aroeauscn aoorso mn ocro aoraranesem, ceonme sresnue:n ace nunceoeeen soeuenceas aromoer seuence an. aermnaor seu me oe mcrooransm encoes a-ermnaa ence, a’ , anor aonuceoe seuencea ra.nso rremceom wnaneooonuceoroeu cconns mruccro aocrcoarnsnm,o w anere on caem mscroo,ra,n osrm.aseen com.r msees aoeaosr oroneucnnoc ae no onu-naeunrea, sa occ murernoo roucn mcrooransma roucnos mcrooransm w eonu o comrsn:ransormn aoo nuceoe seuence ceoe consruc accorno cam, weren sa enome oe mcrooraanssmomsorouosuseo aeneea sse aueonrceon oomeoaoroeues receonme senauencene esrueenesnacvae oreeene mcrooransm. on, weren com.r msees aoeaosr oroneu ecxnre ass neon-neaeurroaoo oucscurornnucoeooe,roucn mcrooransmaransormn aoo roucnos mcrooransm w e sa meo comrsn: o cam, weren sa nuceoe con onuceoe consruc accorn mcrooransm. seuenceoreeerooousenes exressenemc.roo mreanosmsor acroucn aoo , comrsn:rown one or a consorum owo or more row oe mcrocoorrannsmos ca amnrno au ccuounre meum uner cononsa are suaeor roucsrouce e mcrooransms an os soescreneencoroeu ccus,u wree mreenu amoo e. cueur mee meou amc.corno cam,urer comrsn: recovern eoo roucrom me.ume w meoou asccso orne mo ccraoomran,s wmesr oern exreacoono w ans o rercaonvecre sovreonm.e cuure rec. e meo accorno cam or, wereneoo senseran waer, an conovneurou oseecanono, ora csosmvers sees sne.araonrome cuure meum cenruaon, no.ee c mueureo m aeccuomr.no cam, weren aeas aou oeoo s secree o. aoue m.eom ac.corn cam, wereneoo comrses aens o aou. m con.nueou mserooce ascsc.orno cam, werene meoserorme as aac,eac, or o:. a-e mreoxoa acc aocrn mooe carmom, woere canroen aoomosnesn see ecseerreomo ae suroaur a coconsosn m acooeo m ano aece coamers-n nroonx-esae ac moe esereoe suar acoo moe a suar roxa ac moe a suar arcoeo moroex cormourss ense ar meannooe or c aarox en o a- esereoe carox en o a- roxa ac raoacone . moe an aoo eser o aa ac e meo accorno cam, wereneoo comrses a . . oo asrouce accornoe meo o cam. con.sseno o:o a- acrocxorano ac ca mmoe, wroemrenoe coaroon aoms sseneceenro emsereerouo a suara sucoaro a mcooeo m aone ace comaersn- roxa ac moe esereoe suar acoo moe a roxa ac moe a suar no anc-oesoer moee coromxrsrnous esereoe carox en o a- esereoe carox e a manno or araoacone . n o a- roxa ac moe an aoo eser o aa ac . eoo accorno cam, wereneoo s a . a c.aroen n soonu-rncaeu ora ae oacscu orrnne mocorooransams accroorunceo came no,n w-naeruernae occeurrerram o mcr-onoaruaransm ocscunrrcnrea msecronor coamnsamrssoneorvee n non . naura occurrn mcrooransmrom wc e on.eoeo non-nauerrara omcc ourrnuco msecr aosorean casrmo ancc soorurcneso a caoum., wereon aoeue. o a.eas

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