Melatonin Los Ntawm Cov Kabmob, Algae, Thiab Nroj Tsuag Raws Li Txoj Cai Lij Choj Rau Synthetic Melatonin Part 1

Abstract: Melatonin cov khoom noj khoom haus tau siv dav thoob ntiaj teb, nrog cov teb chaws tsim los ua cov neeg siv khoom loj tshaj plaws, nrog kev kwv yees kev loj hlob txhua xyoo ntawm kwv yees li 10 feem pua ​​​​txog 2027, feem ntau hauv cov teb chaws tsim. Kev siv dav ntawm melatonin tiv thaiv kev pw tsaug zog thiab teeb meem tshwj xeeb, xws li dav hlau lag, tau ntxiv rau lwm yam kev siv, xws li kev tiv thaiv kev laus, tiv thaiv kev ntxhov siab, kev tiv thaiv kab mob, tiv thaiv kab mob, thiab lwm yam, uas tau ua rau nws siv, feem ntau. yam tsis muaj tshuaj. Kev lag luam tshuaj tam sim no npog 100 feem pua ​​​​ntawm cov kev xav tau ntawm kev ua lag luam melatonin. Kev tshoov siab los ntawm cov haujlwm uas muaj kev noj qab haus huv ntau dua, muaj peev xwm tau txais melatonin los ntawm cov nroj tsuag, hu ua phytomelatonin, tau tshwm sim ob peb xyoos dhau los. Tsis ntev los no, kev lag luam kws tshuaj tau tsim kho cov kab mob hloov pauv uas nws muaj peev xwm tsim cov tshuaj melatonin hauv bioreactors tau txhim kho. Daim ntawv no tshuaj xyuas cov yam ntxwv ntawm cov tshuaj lom neeg thiab cov khoom sib txuas ntawm melatonin rau tib neeg noj, feem ntau yog kev noj haus ntxiv. Qhov zoo thiab qhov tsis zoo ntawm kev tau txais melatonin los ntawm cov kab mob thiab phytomelatonin los ntawm cov nroj tsuag thiab cov algae raug tshuaj xyuas, nrog rau cov txiaj ntsig ntawm ntuj melatonin, zam tsis txhob siv tshuaj lom neeg los ntawm cov khoom siv tshuaj lom neeg ntawm melatonin. Thaum kawg, cov khoom tshiab no 'kev lag luam thiab kev ua tau zoo, qee qhov uas twb tau ua lag luam, raug tshuaj xyuas.

Glycoside ntawm cistanche tuaj yeem ua rau muaj kev ua haujlwm ntawm SOD hauv plawv thiab daim siab cov ntaub so ntswg, thiab txo cov ntsiab lus ntawm lipofuscin thiab MDA hauv txhua cov ntaub so ntswg, tshem tawm ntau yam reactive oxygen radicals (OH-, H₂O₂, thiab lwm yam) thiab tiv thaiv DNA puas. los ntawm OH-radicals. Cistanche phenylethanoid glycosides muaj peev xwm tshem tawm cov dawb radicals, muaj peev xwm txo tau ntau dua li cov vitamin C, txhim kho cov haujlwm ntawm SOD hauv cov phev ncua, txo cov ntsiab lus ntawm MDA, thiab muaj qee yam kev tiv thaiv ntawm cov phev ua haujlwm. Cistanche polysaccharides tuaj yeem txhim kho kev ua haujlwm ntawm SOD thiab GSH-Px hauv erythrocytes thiab ntsws cov ntaub so ntswg ntawm cov nas senescent sim los ntawm D-galactose, nrog rau txo cov ntsiab lus ntawm MDA thiab collagen hauv lub ntsws thiab ntshav, thiab nce cov ntsiab lus ntawm elastin, muaj Cov nyhuv scavenging zoo ntawm DPPH, ncua lub sijhawm ntawm hypoxia hauv cov nas senescent, txhim kho cov haujlwm ntawm SOD hauv cov ntshav, thiab ncua lub physiological degeneration ntawm lub ntsws hauv kev sim cov nas nrog cellular morphological degeneration, kev sim tau pom tias Cistanche muaj peev xwm antioxidant zoo. thiab muaj peev xwm los ua ib qho tshuaj tiv thaiv thiab kho cov kab mob ntawm daim tawv nqaij laus. Nyob rau tib lub sijhawm, echinacoside hauv Cistanche muaj lub peev xwm tseem ceeb los tshem tawm DPPH dawb radicals thiab tuaj yeem tshem tawm cov pa oxygen reactive, tiv thaiv dawb radical-induced collagen degradation, thiab kuj muaj kev kho zoo ntawm thymine dawb radical anion puas.

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Ntsiab lus: cov khoom noj khoom haus; GMOs; melatonin; kab mob; phytomelatonin; cog raw khoom

1. Taw qhia

Melatonin (N-acetyl-5-methoxytryptamine) is widely used around the world as a  dietary supplement. In general, melatonin is used as a sleep aid supplement, a mild tranquilizer, a generalist antioxidant, and an anticancer and anti-aging component, among others [1]. According to the American Psychiatric Association (APA), approximately one-third of adults suffer from insomnia during their lifetime [2]. It manifests itself in ongoing problems falling asleep and staying asleep. Therefore, it is very likely that the use of synthetic melatonin will spread. In 2019, the global production of synthetic melatonin,  which was around 4000 tons, accounted for around 1.3 billion USD. This vast market is fully assisted by the chemical melatonin, whose synthesis process is very cheap, effective, and,  therefore, lucrative. The melatonin market is expected to grow at a CAGR (compound annual growth rate) of >10 feem pua ​​​​ntawm 5 xyoo tom ntej. Nrog rau qhov kev thov ntau ntxiv no, cov teeb meem insomnia tsim los ntawm COVID-19 kev sib kis tau muaj qhov cuam tshuam zoo [3]. North America muaj kev noj ntau tshaj plaws los ntawm qhov deb, ua raws li Europe. Kev lag luam melatonin thoob ntiaj teb yog tswj hwm los ntawm ob peb lub tuam txhab loj, xws li BASF, Aspen Pharmacare Australia, Nature's Bounty, Pfizer Inc., Natrol LLC, Aurobindo Pharma, thiab Biotics Research Co. Nco ntsoov tias kev noj cov tshuaj melatonin rau kev kho mob cuam tshuam txog. 50 feem pua ​​​​ntawm cov hluavtaws melatonin tsim; tus so muaj tshuaj thiab kev lag luam siv [2,4].

Biologically, melatonin yog ib tug molecule dav faib nyob rau hauv tag nrho cov nceeg vaj ntawm cov kab mob nyob [5]. Pom nyob rau hauv 1958 nyob rau hauv lub pineal caj pas ntawm ib tug nyuj [6] thiab tom qab ntawd nyob rau hauv tib neeg [7], nws yog ib tug ntawm cov feem ntau kawm biomolecules, thiab nws muaj ntau yam functions paub, feem ntau nyob rau hauv cov tsiaj [8,9], tab sis kuj nyob rau hauv cov ntses. [10–12], qaib [13,14], and invertebrates [15]. Hauv cov tsiaj txhu thiab tib neeg lub hlwb, melatonin ua raws li cov tshuaj tiv thaiv antioxidant - lub luag haujlwm tseem ceeb ntawm nws xyoo 1993 [16-18]. Melatonin ua raws li kev tiv thaiv ntawm tes txaus ntshai hauv cov xwm txheej ntxhov siab, nyob rau hauv ntau yam physiological hauv tib neeg, thiab, raws li ntau yam kev tshawb fawb, muaj txiaj ntsig kev txhim kho ntawm cov kab mob sib txawv thiab kev ua haujlwm tsis zoo. Daim duab 1 qhia txog qee qhov kev tiv thaiv thiab kev tswj hwm ntawm melatonin hauv tib neeg thiab nthuav tawm melatonin raws li kev nthuav dav pleiotropic molecule, sawv tawm vim nws qhov cuam tshuam, lub luag haujlwm ntawm melatonin hauv kev tswj cov lipid thiab qabzib metabolism, ua rau cov insulin tsis kam noj hmo thiab hnub so. rhiab heev. Cov txiaj ntsig no zoo li cuam tshuam nrog kev yoo mov thaum hmo ntuj thiab noj diurnal, tiv thaiv kev hnyav hnyav [19]. Peb kuj tseem hais txog nws lub luag haujlwm ua tus neeg sawv cev tiv thaiv oncogenic, inhibiting kev loj hlob, kev loj hlob, thiab metastasis ntawm ntau cov qog. Kev kho mob ntawm cov qog nrog melatonin txhim kho chemo- thiab radiotherapy rhiab heev, ua raws li kev sib koom ua ke hauv kev tswj cov qog nqaij hlav cancer. Tsis tas li ntawd, melatonin txo qis kev puas tsuaj rau lub cev ib txwm muaj, tiv thaiv lawv tiv thaiv cov tshuaj toxicity, tejzaum nws los ntawm kev txhim kho lub cev tiv thaiv kab mob [20–22]. Ntawm cov kev ua haujlwm tsis zoo thiab cov kab mob uas tau kawm txog cov txiaj ntsig zoo ntawm melatonin yog cov paj hlwb, xws li Alzheimer's, Parkinson's, fibromyalgia, kev nyuaj siab, kev tsis txaus siab tsis txaus ntseeg, kev puas siab puas ntsws, thiab migraines; Cov teeb meem mob plawv, suav nrog hypercholesterolemia, kub siab, metabolic syndrome, thiab glycemic tsis txaus; cov teeb meem kev noj qab haus huv hauv plab, xws li gastroesophageal reflux, ulcers, thiab chim siab plob tsis so tswj syndrome; Cov teeb meem kev tiv thaiv kab mob, xws li ntau yam kab mob sclerosis, autoimmune teb (kev ntxhov siab kis las, kev nyuaj siab lom, psoriasis, thiab lwm yam), sepsis, COVID-19, thiab lwm yam. [3,23–26]; thiab kuj osteopenia [27], sarcopenia [28], pre-eclampsia, fertility, polycystic zes qe menyuam syndrome, thiab menopause, thiab lwm yam [29–32]. Txawm li cas los xij, txawm hais tias melatonin yog ib qho molecule uas tau kawm dav txij li xyoo 1950, cov kev tshawb fawb tau ua tiav yuav tsum muaj kev soj ntsuam ntau dua thiab kev sim ob qhov muag tsis pom kev los piav qhia nws qee zaum tsis meej pem pleiotropic ua [33,34].

Txawm li cas los xij, melatonin paub zoo tias yog cov tshuaj hormones uas tswj kev pw tsaug zog. Nws cov qib oscillating nyob rau hauv cov ntshav ntws raws li lub sij hawm ntawm lub teeb thiab tsaus ntuj (circadian rhythms) vim qhov tso tawm ntawm melatonin los ntawm lub caj pas pineal yog ib qho ntawm feem ntau kawm thiab paub txog ntawm no molecule. Kev nce qib ntawm cov ntshav melatonin thaum thawj lub sijhawm pw tsaug zog mus txog 150-220 tus ncej / mL ua rau kev pib pw tsaug zog, txo qis kev pw tsaug zog latency thiab fragmentation thiab nce pw tsaug zog ntev thiab zoo [1,35,36]. Melatonin ua raws li kev sib koom ua ke ntawm lub circadian pw tsaug zog-tsim lub voj voog thiab lub caij nyoog sib dhos. Hauv qhov kev nkag siab no, ntau yam kev pw tsaug zog tau raug kho nrog melatonin, suav nrog kev pw tsaug zog qeeb, hmo ntuj ua haujlwm pw tsaug zog tsis zoo, muaj kev cuam tshuam rau lub caij nyoog, kev pw tsaug zog hauv qhov muag tsis pom kev thiab kev laus, thiab cov kab mob pathophysiological ntawm cov menyuam yaus, nrog kev txhim kho tseem ceeb hauv kev pw tsaug zog zoo [ 37–41] ib. Qhov teeb meem loj tshaj plaws uas kho nrog melatonin yog lub dav hlau lag-ib ntus hauv kev pw tsaug zog-tsim suab nrov tom qab kev sib tw hla dej hiav txwv [42-45]. Tej zaum, qhov tseem ceeb hauv kev tshawb fawb txog nws lub luag haujlwm ua tus tswj kev pw tsaug zog tau ua rau tsis muaj kev tshawb fawb txog nws txoj haujlwm ua tau nyob rau hauv ntau lwm yam physiological thiab kev kho mob.

Melatonin nyob rau hauv cov nroj tsuag, thiaj li hu ua phytomelatonin, tau tshawb pom ib txhij los ntawm peb pawg tshawb fawb hauv ntau hom khoom cog hauv xyoo 1995 [46–48]. Lub sij hawm phytomelatonin, uas yog hais txog melatonin ntawm zaub keeb kwm (cov nroj tsuag thiab algae), yog siv los sib txawv ntawm cov tsiaj thiab / los yog hluavtaws melatonin. Lo lus no yog dav heev thiab yog siv tsis tu ncua nyob rau hauv kev tshawb fawb ntawm phytochemistry, cog physiology, botany, zaub mov chemistry, thiab lwm yam, ntawm cov nroj tsuag melatonin. Hauv cov nroj tsuag, phytomelatonin kuj yog ib qho pleiotropic molecule, nthuav tawm ntau lub luag haujlwm hauv ntau lub cev cov lus teb (Daim duab 1). Kev tswj hwm los ntawm melatonin ntawm cov khoom xws li photosynthesis, suav nrog stomatal CO2 uptake thiab dej kev lag luam, carbohydrate, lipid, nitrogen, thiab sulfur metabolism, thiab yooj yim phenol, flavonoid, thiab terpenoid metabolism, tau ua kom pom qhov tseem ceeb hauv cov txheej txheem ntawm kev cog qoob loo. (germination, cog kev loj hlob, rooting, branching, thiab lwm yam) thiab kev loj hlob ntawm cov me nyuam, nrog rau fertility, parthenocarpy, noob thiab txiv hmab txiv ntoo kev loj hlob, ripening, senescence, thiab kev txuag ntawm txiv hmab txiv ntoo thiab txiav paj [49-53]. Feem ntau, melatonin tswj cov txheej txheem no los ntawm kev ua ntawm cov nroj tsuag hormone network, nce / downregulating ob peb biosynthesis, catabolic, thiab transcription yam uas yog cog cov tshuaj hormones [54-56]. Ib qho ntawm qhov zoo tshaj plaws agronomic thiab biotechnological txaus siab yog lub luag haujlwm ntawm phytomelatonin ua tus txhawb nqa kev ua siab ntev tiv thaiv biotic thiab abiotic stresses [57–68] (Daim duab 1). Tam sim no, phytomelatonin tau nthuav tawm ua cov cuab yeej zoo nkauj hauv eco-phooj ywg los tswj cov kab mob lom thiab pab txhawb kev tiv thaiv / hloov pauv ntawm cov nroj tsuag rau / tawm tsam kev hloov pauv huab cua.

2. Biosynthesis ntawm Melatonin

Melatonin yog ib qho acetylated compound tau los ntawm serotonin. Ob leeg indolic amines yog synthesized los ntawm cov amino acid tryptophan nyob rau hauv ib txoj kev biosynthetic uas tau kawm ntau nyob rau hauv ob qho tib si tsiaj thiab nroj tsuag [69,70]. Hauv cov nroj tsuag, tryptophan hloov mus rau hauv tryptamine los ntawm enzyme tryptophan decarboxylase (TDC) (Daim duab 2). Tryptamine yog tom qab ntawd hloov mus rau hauv 5-hydroxytryptamine (serotonin) los ntawm tryptamine 5-hydroxylase (T5H), ib qho enzyme uas tau kawm ntau hauv mov, thiab uas tuaj yeem ua nrog ntau cov substrates, txawm tias qhov no tsis tau kawm. hauv qhov tob. Serotonin yog N-acetylated los ntawm serotonin N-acetyltransferase (SNAT). N-acetylserotonin ces methylated los ntawm acetylserotonin methyl transferase (ASMT)-ib hydroxy indole-O-methyltransferase-uas ua rau melatonin. Hauv cov nroj tsuag, cov tshuaj methylation ntawm N-acetylserotonin tuaj yeem ua tau los ntawm caffeic acid O-methyltransferase (COMT), chav kawm ntawm cov enzymes uas tuaj yeem ua rau ntau yam substrates, suav nrog caffeic acid thiab quercetin [71]. Serotonin kuj tseem tuaj yeem hloov mus rau hauv 5-methoxy tryptamine los ntawm ASMT/COMT los tsim melatonin tom qab qhov kev ua ntawm SNAT. Txoj kev no yuav tshwm sim nyob rau hauv senescence thiab/los yog kev nyuaj siab [70,72]. Tsis tas li ntawd, melatonin tuaj yeem tsim los ntawm kev tsim N-acetyl tryptamine los ntawm SNAT, uas yuav hloov mus rau N-acetylserotonin los ntawm T5H [73], txawm hais tias txoj kev no tsis tau pom, tej zaum vim T5H yog qhov tsawg tshaj plaws ntawm kev kawm enzyme ntawm txoj kev. (Daim duab 2). Qhov zoo siab, txog li plaub lub noob encoding histone deacetylases (DAC) tau raug txheeb xyuas hauv cov nplej nplej uas tuaj yeem thim rov qab cov kauj ruam ntawm serotonin mus rau N-acetylserotonin thiab los ntawm 5-methoxy tryptamine rau melatonin. DAC, qhia nyob rau hauv chloroplast, nthuav tawm enzyme kev ua rau N-acetylserotonin, N-acetyl tryptamine, thiab melatonin, nrog rau siab tshaj deacetylase kev ua si rau N-acetyl tyramine [74].

Hauv cov tsiaj hlwb, serotonin yog tsim los ntawm 5-hydroxytryptophan tom qab ua ntu zus ntawm tryptophan hydroxylase (TPH) thiab TDC. Txawm hais tias TPH tsis tau raug kuaj pom hauv cov nroj tsuag, muaj 5-hydroxytryptophan qhia tias qee qhov kev ua haujlwm enzymatic, xws li TPH, ua rau tsawg dua hauv cov nroj tsuag. Tsis tas li ntawd, melatonin tuaj yeem tsim los ntawm kev tsim ntawm 5-methoxy tryptamine, feem ntau nyob rau hauv kev ntxhov siab raws li tau hais los ntawm ntau tus kws sau ntawv, qhia tias txoj kev melatonin biosynthesis tuaj yeem ua raws ntau txoj hauv kev piv nrog cov tsiaj hlwb, muaj peev xwm hloov tau ntau dua. rau metabolic kev hloov hauv cov nroj tsuag [72,75]. Tag nrho cov npe enzymes tau kuaj pom thiab pom muaj nyob hauv nplej thiab Arabidopsis, tshwj tsis yog TPH, uas paub zoo hauv cov tsiaj tab sis tsis nyob hauv cov nroj tsuag. Txawm li cas los xij, qee tus kws sau ntawv tau hais tias T5H tuaj yeem ua raws li hydroxylase nrog qis substrate tshwj xeeb thiab muaj peev xwm ua yeeb yam hauv txhua qib hydroxylation tau piav qhia [70,76–79]. Tib qhov dav substrate tshwj xeeb no tuaj yeem raug ntaus nqi rau SNAT, ASMT, thiab COMT enzymes. Melatonin intermediates yog tsim nyob rau hauv ntau yam subcellular compartments, xws li cytoplasm, endoplasmic reticulum, mitochondria, thiab chloroplasts, uas txiav txim siab cov theem tom ntej enzymatic [80,81].

Hauv cov kab mob, muaj ob peb txoj kev tshawb fawb ntawm melatonin biosynthesis txoj kev [82]. Saccharomyces thiab kab mob (Geobacillus, Bacillus, thiab Pseudomonas) tsim cov serotonin thiab melatonin ntawm ntau qhov sib txawv [83–89]. Tsis tas li ntawd, kev tsim cov melatonin tau ua pov thawj los ntawm lwm tus kws sau ntawv hauv kab lis kev cai ntawm cov poov xab Pichia kluyveri, Saccharomyces cerevisiae, thiab S. uvarum thiab cov kab mob (Agrobacterium, Pseudomonas, Variovorax, Bacillus, thiab Oenococcus) [85, 90] dhau los, 9. Hauv cov kab mob photosynthetic Rhodospirillum rubrum [92] thiab Erythrobacter longus [93] thiab Escherichia coli [94].

Hauv cov poov xab Saccharomyces cerevisiae, tsis zoo li hauv cov nroj tsuag thiab tsiaj txhu, zoo li biosynthesis ntawm 5-hydroxytryptophan los ntawm tryptophan tsis tshwm sim. Interestingly, ob peb theem tau piav qhia zoo li yuav thim rov qab hauv S. cerevisiae, xws li ntawm 5-hydroxytryptophan thiab serotonin, N-acetylserotonin thiab melatonin, thiab 5-methoxy tryptamine thiab melatonin [90,95], raws li tau piav qhia hauv daim duab 2. Hauv Bacillus amyloliquefaciens SB-9 thiab Pseudomonas fluorescens RG11, 5- hydroxytryptophan, serotonin, thiab N-acetylserotonin, tab sis tsis kuaj pom tryptamine [85,{12}}]. Yog li, ntau cov noob ntawm cov kab mob hauv paus chiv keeb tau siv los tsim cov kab mob melatonin-ua Escherichia coli. Piv txwv li, DDC gene, encoding ib qho aromatic L-amino acid decarboxylase los ntawm Candidatus Koribacter ntau yam Ellin 345 thiab Draconibacterium orientale, thiab AANAT gene, encoding alkylamine N-acetyltransferase los ntawm Streptomyces griseofuscus, tau assayed [9]. Undoubtedly, xav tau kev tshawb fawb ntxiv los piav qhia txog txoj hauv kev biosynthetic tiav ntawm melatonin hauv cov kab mob prokaryotic thiab eukaryotic sib txawv [82].

3. Biological Melatonin piv rau Synthetic Melatonin

Thaum pib, melatonin tau txais rau kev sim thiab kev tshawb fawb soj ntsuam los ntawm cov tsiaj txhu (tsuas yog los ntawm pineal caj pas thiab cov zis), nrog rau qhov kev pheej hmoo ntawm kev kis kab mob [98,99]. Cov tswv yim no tau raug tshem tawm thaum melatonin tuaj yeem tau los ntawm cov tshuaj synthesis [100]. Tam sim no, tag nrho cov melatonin siv rau kev lag luam thiab kev kho mob yog tau los ntawm kev siv tshuaj synthesis. Cov txheej txheem no, uas tau nthuav tawm cov teeb meem loj hauv xyoo 1980s, suav nrog kev tuag vim muaj cov khoom siv los ntawm cov khoom sib txuas los ntawm tryptophan [101], muaj kev nyab xeeb thiab muaj txiaj ntsig ntau dua niaj hnub no. Txawm li cas los xij, kev npaj melatonin tau piav qhia txog qhov muaj tag nrho ntawm cov khoom siv tsis zoo vim lawv cov tshuaj lom neeg. Daim duab 3 qhia peb ntawm feem ntau siv tshuaj synthesis txoj kev rau melatonin thiab cov by-products uas yog generated nyob rau hauv nws synthesis [102]. Lub synthesis ntawm melatonin los ntawm tryptophan derivatives (Daim duab 3, Scheme A) tsim tshuaj lom los ntawm cov khoom uas muaj qee zaum ua rau cov kab mob tseem ceeb, xws li eosinophilia-myalgia syndrome [101,103,104], thaum txoj kev tam sim no feem ntau (Daim duab 3, Scheme B) rau synthesis ntawm melatonin los ntawm phthalimide [105] tsa ib qho kev tsis txaus ntseeg tseem ceeb txog kev toxicity ntawm ob peb ntawm cov khoom lag luam uas tau tsim [106]. Tsis tas li ntawd, Fischer indole cov tshuaj tiv thaiv los ntawm allylamine (Daim duab 3, Scheme C) tam sim no txaus ntshai thiab tshuaj lom reactants [107].

Ntawm qhov tod tes, tau txais melatonin los ntawm cov khoom siv tsis yog tsiaj txhu tau nthuav tawm raws li kev cog lus muaj zog rau yav tom ntej, tsis yog los hloov cov khoom siv hluavtaws melatonin tab sis ua kom muaj txiaj ntsig zoo dua qub, thiab lwm qhov chaw [108].

4. Cov tswv yim kom tau cov tshuaj lom neeg Melatonin

Melatonin muaj nyob rau hauv txhua hom kab mob uas paub txog, los ntawm prokaryotes mus rau eukaryotes, suav nrog cov poov xab, algae, fungi, thiab nroj tsuag, nrog rau tsiaj txhu [80,109–111]. Hauv qab no, cov txheej txheem tsim nyob rau hauv cov kab mob thiab cov nroj tsuag raws li qhov ua tau ntawm ntuj melatonin tau nthuav tawm.

4.1. Melatonin los ntawm cov kab mob

ib. Saccharomyces

Thawj txoj hauv kev rau kev tsim cov tshuaj lom melatonin tsis ntev los no tau ua los ntawm ib pab pawg ntawm Danish kws tshuaj lub tuam txhab Novo Nordisk siv cov kev hloov kho genetic Saccharomyces cerevisiae (Table 1, khoom #1). Cov neeg German thiab cov neeg ua haujlwm sib koom ua ke tau tsim ib txoj hauv kev sib txuas ntawm melatonin hauv ib hom kab mob ntawm cov poov xab uas muaj cov noob heterologous encoding ob peb melatonin biosynthesis enzymes thiab co-factor-supporting pathways [112]. Cov poov xab transgenic codified txawv cov noob los ntawm Rattus norvegicus, Lactobacillus ruminis, Pseudomonas aeruginosa, Homo sapiens, Schistosoma mansoni, Bos Taurus, thiab Salmonella enterica. Pub cov poov xab tsuas yog qabzib thiab acetyl Co-A, melatonin ntau lawm mus txog 14.5 mg·L −1 ntawm 76 h. Txawm li cas los xij, raws li lwm tus kws sau ntawv, qee qhov teeb meem, xws li N-acetylserotonin tsub zuj zuj hauv cov poov xab, tsis sib npaug ntawm cov noob qhia, thiab kev txheeb xyuas qee cov tshuaj lom neeg nruab nrab, yuav tsum tau hais txog [113].

b. Escherichia coli

Hauv kev ua thib ob, lub sijhawm no siv cov kab lis kev cai hloov pauv hloov pauv Escherichia coli kab lis kev cai (Table 1, khoom #2), Novo Nordisk tau tshaj tawm cov tshuaj lom melatonin tsim los ntawm cov kab mob heterologous tsim los ntawm recombinant E. coli, suav nrog ntau cov noob xws li TDC gene. los ntawm Candidatus Koribacter ntau yam, SNAT gene los ntawm Streptomyces griseofuscus, thiab tib neeg ASMT gene. Tsis tas li ntawd, qee cov noob caj noob ces uas muaj cov tryptophan tau raug thaiv lossis tshem tawm kom tsis txhob muaj kev tsim txom, kev puas tsuaj, thiab kev thauj mus los [96,97]. Tom qab ob peb txoj kev txhim kho thiab pub mis nrog cov ntxhia ntsev, cov vitamins, thiab tshuaj tua kab mob, cov kab mob hauv lub cev tsim cov tshuaj melatonin ntawm ~ 1 g·L −1 siv cov piam thaj ua cov pa roj carbon monoxide thiab txog li 2 g·L −1 hauv tryptophan-fed cells, nrog cov qib tsis txaus ntseeg ntawm cov khoom lag luam. Yog li, raws li cov kws sau ntawv, cov GMO E. coli hom kab mob no yuav yog lub hauv paus rau yav tom ntej kev lag luam lom melatonin ntau lawm siv microbial cell factories. Txawm li cas los xij, kev siv cov kab mob transgenic los tsim cov tshuaj rau tib neeg noj tuaj yeem muaj teeb meem thaum lub hom phiaj yog coj cov khoom ntuj tsim los rau cov neeg siv khoom zoo lossis cov neeg siv khoom tiv thaiv GMO.

c. Cov kab mob lactic acid

Melatonin kuj tau tsim muaj kev lag luam los ntawm microbial fermentation, raws li qhia hauv [114]. Melatonin biosynthesis tau qhia los ntawm ntau hom kab mob lactic acid, xws li Lactobacillus sp. (L. brevis, acidophilus, bulgaricus, casei subspecies. sake, fermentum, helveticus subspec. jogorti, plantarum); Bifidobacterium sp. (B. breve spp. breve, longum spp. infantis); Enterococcus sp. (E. faecalis TH10); thiab Streptococcus thermophilus. Cov khoom tsim los ntawm cov thev naus laus zis no tau muag los ntawm Quantum Nutrition Labs (Texas, USA) raws li Melatonin Drops, Qultured™, muaj 8 mg ntawm poov xab melatonin (Table 1, khoom #3).

d. Chlorella

Ib yam khoom uas ua los ntawm algae yog Herbatonin® (Table 1, khoom #4), formulated nyob rau hauv cov ntsiav tshuaj muaj 0.3 los yog 3 mg ntawm phytomelatonin, txawm nyob rau hauv Teb chaws Europe nws yog marketed nyob rau hauv koob tshuaj ntawm 0.3 thiab 1.9 mg, raws li EU txoj cai. Qhov no formulation muaj ntau hom nroj tsuag xws li mov (Oryza sativa L.) thiab alfalfa (Medicago sativa L.), ua ke nrog ntsuab alga Chlorella pyrenoidosa thiab C. vulgaris. Peb cov ntaub ntawv qhia tau hais tias cov microalgae no muaj tsis ntau tshaj 2-15 ng·g DW-1 [115], thiab tus khub cog hom muaj tsawg heev ntawm phytomelatonin, 1-5 ng·g−1 hauv mov thiab 16 ng·g. −1 nyob rau hauv alfalfa [116]. Lub xub ntiag ntawm Chlorella qhia tias phytomelatonin feem ntau tau txais los ntawm culturing ntsuab algae nyob rau hauv bioreactors, tejzaum nws pub nrog precursors xws li tryptophan, zoo ib yam li ntawd nyob rau hauv Achillea millefolium [117], txawm hais tias tsis muaj cov ntaub ntawv luam tawm ntawm txoj kev. tau txais cov phytomelatonin-nplua nuj rho tawm, tsuas yog lawv cov cim biochemical [118]. Tseem tsis muaj cov ntaub ntawv hais txog kev tswj xyuas qhov muaj cyanotoxins hauv cov tshuaj no vim muaj cov kab mob kis tau los ntawm cyanobacteria (xiav-ntsuab algae). Cov cyanotoxins no muaj ntau yam tsis xav tau cuam tshuam txog carcinogenicity, hepatotoxicity, thiab neurotoxicity, thiab lwm yam. Yog li, kev tshawb pom ntawm cyanotoxins hauv qee cov tshuaj noj algal ntxiv dag zog rau kev xav tau kev tswj hwm zoo [119,120].

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