Abstract
Selenocysteine (Sec) is the 21st non-standard proteinogenic amino acid. Due to the particularity of the codon encoding Sec, the selenoprotein synthesis needs to be completed by unique mechanisms in specific biological systems. In this paper, the underlying mechanisms for the biosynthesis and incorporation of Sec into selenoprotein were comprehensively reviewed on five aspects: (i) the specific biosynthesis mechanism of Sec and the role of its internal influencing factors (SelA, SelB, SelC, SelD, SPS2 and PSTK); (ii) the elements (SECIS, PSL, SPUR and RF) on mRNA and their functional mechanisms; (iii) the specificity (either translation termination or translation into Sec) of UGA; (iv) the structure–activity relationship and action mechanism of SelA, SelB, SelC and SelD; and (v) the operating mechanism of two key enzyme systems for inorganic selenium source flow before Sec synthesis. Lastly, the size of the translation initiation interval, other action modes of SECIS and effects of REPS (Repetitive Extragenic Palindromic Sequences) that affect the incorporation efficiency of Sec was also discussed to provide scientific basis for the large-scale industrial fermentation for the production of selenoprotein.
Highlights
At present, there are 22 kinds of amino acids involved in protein biosynthesis
SECIS elements in eukaryotes and prokaryotes are similar in structure, but the former ones are distributed outside the 3 -untranslated region (3 -UTR) of selenoprotein mRNA [31,32], located far downstream of UGA, and have a relatively large sequence [33]
The above major mechanisms affecting the incorporation of Sec mainly focus on the key factors such as SelA–SelD and SECIS, which lead to the traditional biosynthesis of selenoprotein
Summary
As one key catalytic amino acid residue of Glutathione peroxidase (GPx), Thioredoxin reductase (TrxR), Selenoprotein P (SELENOP) and some others, Sec involves such physiological activities as anti-aging, anti-inflammation, anti-cancer, detoxification, maintenance of cardiovascular health, improvement of immunity and fertility [4] These biological functions are mainly carried out by selenases which are the catalytically active form of selenoproteins only by incorporating Sec as the catalytic residue on the active site. Molecules 2021, 26, 7120 incorporating Sec as the catalytic residue on the active site In this regard, this paper firstly discussed the pathway of Sec biosynthesis and the influence of its internal components, pdoisincutesdseodutthbeopthatihmwpaoyrtaonf tSfeaccbtoiorssyanntdheesleismaenndtsthafefeinctflinugenthcee oinfciotsrpinotreartnioanl coofmSepco, nents, and anthaelynzpedoitnhteeidr aocuttiobnomtheicmhapnoirstmanstaffatecrtowrasradnsd, weiltehmaevniteswaftfoecptrinomg tohtienigntchoerpsyonrathtieotnicof Sec, efficieanncdy aonf asleyleznedopthroetieriancatinodn tmheecshuabnsiesqmusenafttienrdwuasrtdrisa, lwpirtohdauvciteiown.to promoting the synthetic efficiency of selenoprotein and the subsequent industrial production. 2.2.TThhee mSyencthhaensiissmMsecohfanSiescmsoyfnSthecesinisEiunkeaurykoatresyoanteds,thaercRhoaleeaofaPnSdTKpraonkdarSyBoPt2eswaitrheinquItite similarT, heexcmepetchfoarniasmfeswodf iSffeecresynnceths.eOsisneindeifufkeraernycoeteiss,tahracthtaheea paonsditpiornokaanrdyostterus catruerequoifte SEsCimISilaorn, esxecleenpot pforor taeifnewmdRiNffAereanrceessi.gOninfeicadniftfleyredniscteinisctt.hAatntohteheprodsiitfifoenreanncde isstrtuhcatturtheeof traSnEsClaIStioonnesleolnegnaotpiorontfeainctomrRisNdAefianreedsiagsnSiefilcBan[1t8ly,1d9]isitninpcrto. kAarnyoottheesrwdhififleereeEnFceSeics [t1h9a,t20th] e intreaunksalarytiootnesehloansgsalitgiohntlfyacdtioffreirsednet fistnreudctausreSse.lBTh[1e8t,h1i9r]dindipffreorkeanrcyeoitsetshwathaildedeiEtiFoSneacl [s1te9p,2s0] foirntweuokparryootetaessehsaasrselrigehqutliyreddif[f2e1re],nstusctrhuacstuPrSeTs.KT(hOe-pthhiordspdhioffseerreynlc-etRisNtAha[Stera]Sdecdkiitnioansea)l asntedps SBfoPr2t(wSoECprISo-tbeainsedsinagreprreoqtueiirned2)[,2b1e]s, isduecshSaeslCPS, STeKrS(O, S-eplhAos(SpehcoSs)e,raynl-dtRSNelAD[S(eSrP]SSec2,kainkaisned) aonfd seSleBnPo2p(rSoEteCiInS-[b2i2n])d.iPnSgTpKroptehions2p)h, obreysliadteessStheleCh, ySderrSo,xSyelloAn(SSeecr-St)R, NanAd[SSere]SleDc a(nSdPSc2o,navekrintsditof tosSeleePn-otRpNroAte[iSner][Se2c2[]1)9. ]P, SwThKicphhiosscpohnovreyrltaetdestothSeehc-ytdRrNoxAy[Sleor]SnecSbeyr-SteRcNSAaf[Steerr]wSeac radnsd[2c3o,n2v4e].rtIsnit adtodiStieoPn-,tRSNBPA2[,Searn]Se8c4[619a]m, winhoicahciids cpornovteeirntefdoutondSeicn-tyReNasAt,[Siesr]aSnecobthyeSreicmSpaoftretarwntafradcsto[2r3a,2f-4]. feIcntinadgdtihteiosny,nStBhPe2si,saonf8S4e6caimn ienuokaacriydopterso.tAeifntefroucenrdtaiinn yfeoaldstin, igs, aSnBoPt2hecrainmipnoterrtaacntt wfaictthor eEaFffSeecctitnogptrhoemsoytenthraensisslaotifonSeecxtiennesiuokna,raynodteist.alsAoftcearncaevrotaidinthfoeltdeirnmgi,nSaBtiPon ocfantrainstelarta-ct inwg iatthUeGEFAS.eAcstoshporwomn ionteFitgraunresl2at[i1o,n13e],xitnenthsieoenu, kaanrdyoitiaclSseocceaxnparevsosidonthpeatthewrmayin,aStEioCnISof intrthanesdlaotwinngsatrteUamGAu.nAtrsasnhsolawtendinpaFritgoufrem2R[N1,A13b],inindsthfeirestutkoarSyBoPt2ic, wSehciechxpirnetsusironnbpinadthswtoay, eESFESCeIcSpinrottheeind. oewEnFSsterceapmreusenntrtsantshleatreedcrpuairttedof SmecR-NtRANAbi[nSedr]Ssecfitrost tthoeSBUPG2A, wchoidchoninatnudrn mbaiknedssitobienEdFSweicthprtohteeignr.oewEiFnSgeacmpriensoenactsidthcehareincrtuoitfeadciSlietac-tteRtNheAs[ySenr]tSheec stios tohfenUewGAeuckoadro-n yoatnicdsmeleankoespriot tbeiinnd. with the growing amino acid chain to facilitate the synthesis of new eukaryotic selenoprotein
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