{"id":5806,"date":"2024-08-04T21:25:24","date_gmt":"2024-08-04T21:25:24","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=5806"},"modified":"2024-08-04T21:25:24","modified_gmt":"2024-08-04T21:25:24","slug":"streptomyces-using-non-directed-activation-silencing-gene-clusters","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/da\/streptomyces-using-non-directed-activation-silencing-gene-clusters\/","title":{"rendered":"Forskningsfremskridt inden for udvinding af aktive sekund\u00e6re metabolitter fra Streptomyces ved hj\u00e6lp af genklynger med ikke-rettet aktiveringssl\u00f8ring"},"content":{"rendered":"<p>Forskningsfremskridt inden for udvinding af aktive sekund\u00e6re metabolitter fra Streptomyces ved hj\u00e6lp af genklynger med ikke-rettet aktiveringssl\u00f8ring<br \/>\nMikrobielle sekund\u00e6re metabolitter er en klasse af strukturelt forskellige, funktionelt komplekse og biologisk aktive stoffer, som spiller en vigtig rolle i forskning og udvikling af l\u00e6gemidler. P\u00e5 nuv\u00e6rende tidspunkt er der identificeret ca. 300.000 forbindelser fra mikroorganismer, hvoraf over 60% af antibiotika stammer fra Streptomyces. Men med isoleringen af et stort antal sekund\u00e6re metabolitter er sandsynligheden for at opdage antibiotika med betydelig biologisk aktivitet og nye strukturer fra Streptomyces faldende. I de senere \u00e5r, med den udbredte anvendelse af genomsekventeringsteknologi i mikrobiel sekventering, er en stor m\u00e6ngde Streptomyces-genomoplysninger blevet offentliggjort. Gennem bioinformatisk analyse af Streptomyces-genomdata blev det konstateret, at en stor del af generne stadig er i en tavs tilstand, hvilket indikerer, at der stadig er et stort antal potentielle sekund\u00e6re metabolitter, som ikke er blevet opdaget. P\u00e5 grund af konventionelle dyrkningsforhold er de biosyntetiske genklynger i Streptomyces ikke blevet effektivt aktiveret, hvilket resulterer i, at deres unikke metaboliske veje ofte udtrykkes mindre eller slet ikke. Derfor er det af stor betydning at udforske nye aktive sekund\u00e6re metabolitter ved at aktivere den tavse genklynge i Streptomyces.<br \/>\nFor at aktivere udtrykket af d\u00e6mpende gener i Streptomyces og opdage mere aktive sekund\u00e6re metabolitter er der indtil videre blevet udviklet og anvendt forskellige metoder til at aktivere d\u00e6mpende genklynger. De almindeligt anvendte strategier kan inddeles i to kategorier: Den ene er ikke-rettet aktiveringsstrategi, som f\u00e5r Streptomyces til at producere forskellige metabolitter ved at \u00e6ndre sammens\u00e6tningen af kulturmediet (kulstofkilde, kv\u00e6lstofkilde, sporstoffer, kemiske aktivatorer), stammens v\u00e6kstmilj\u00f8 (temperatur, pH, beluftning, beholdertype) eller mikrobiel samkultur; En anden type er m\u00e5lrettet aktiveringsstrategi, som bruger genredigeringsteknologi (CRISPR-Cas9), m\u00e5lrettet aktivering af specifikke genklynger (promoter engineering, pathway specific regulatory factor activation, heterologous expression) og andre midler til at muligg\u00f8re ekspression af d\u00e6mpede gener i Streptomyces. Sammenlignet med m\u00e5lrettede aktiveringsstrategier kr\u00e6ver ikke-m\u00e5lrettede aktiveringsstrategier ikke etablering af et genetisk manipulationssystem for m\u00e5lstammen, og de har s\u00e5ledes fordelene ved enkel betjening og evnen til samtidig at aktivere flere biosyntetiske genklynger (i stedet for en specifik biosyntetisk genklynge), hvilket g\u00f8r dem mere bredt anvendelige. Denne artikel giver et kort overblik over ikke-rettede aktiveringsstrategier for silencing-gener i Streptomyces, s\u00e5som \u00e6ndring af sammens\u00e6tningen af kulturmediet eller kulturbetingelserne, samkulturstrategier, tils\u00e6tning af kemiske aktivatorer og global regulering (se figur 1), og beskriver de problemer, man st\u00e5r over for, og de fremtidige udviklingsmuligheder inden for dette omr\u00e5de.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5807\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-177.png\" alt=\"\" width=\"800\" height=\"315\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-177.png 800w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-177-768x302.png 768w\" sizes=\"(max-width: 800px) 100vw, 800px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5808\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-163.png\" alt=\"\" width=\"806\" height=\"424\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-163.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-163-768x404.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5809\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-153.png\" alt=\"\" width=\"806\" height=\"382\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-153.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-153-768x364.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5810\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-137.png\" alt=\"\" width=\"806\" height=\"692\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-137.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-137-768x659.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5811\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-124.png\" alt=\"\" width=\"806\" height=\"734\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-124.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-124-768x699.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-124-791x720.png 791w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5812\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-114.png\" alt=\"\" width=\"806\" height=\"352\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-114.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-114-768x335.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5813\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-104.png\" alt=\"\" width=\"806\" height=\"312\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-104.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-104-768x297.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5814\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-95.png\" alt=\"\" width=\"806\" height=\"498\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-95.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-95-768x475.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5815\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/9-89.png\" alt=\"\" width=\"806\" height=\"561\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/9-89.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/9-89-768x535.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5816\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/10-71.png\" alt=\"\" width=\"806\" height=\"646\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/10-71.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/10-71-768x616.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-5817\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/11-65.png\" alt=\"\" width=\"806\" height=\"285\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/11-65.png 806w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/11-65-768x272.png 768w\" sizes=\"(max-width: 806px) 100vw, 806px\" \/><br \/>\nOpdagelsen af antibiotika er en vigtig milep\u00e6l i den medicinske udviklings historie og har i h\u00f8j grad reduceret forekomsten og d\u00f8deligheden af bakterielle infektioner. I \u00f8jeblikket produceres omkring 60% af de opdagede antibiotika af Streptomyces. Men med den udbredte brug af antibiotika bliver resistens- og superbug-problemer stadig mere fremtr\u00e6dende. For at l\u00f8se problemerne med l\u00e6gemiddelresistens og superbugs er vi n\u00f8dt til at udforske nye antibiotika. Gennem bioinformatisk analyse af Streptomyces-genomdata blev det konstateret, at en betydelig del af generne er i en tavs tilstand. Derfor er aktivering af tavse genklynger i Streptomyces et af de vigtigste sp\u00f8rgsm\u00e5l p\u00e5 nuv\u00e6rende tidspunkt. Flere og flere forskere har bem\u00e6rket Streptomyces' potentiale til at opdage nye forbindelser og er begyndt at unders\u00f8ge, hvordan man kan stimulere aktiveringen af tavse genklynger.<\/p>\n<p>Baseret p\u00e5 om m\u00e5lgenet for aktivering er klart, opdeler vi de nuv\u00e6rende aktiveringsstrategier i rettede aktiveringsstrategier og ikke-rettede aktiveringsstrategier. Ikke-rettede aktiveringsstrategier omfatter aktiveringsstrategier, der \u00e6ndrer sammens\u00e6tningen af eller betingelserne for dyrkningsmediet, strategier for samdyrkning, tils\u00e6tning af kemiske aktivatorer og global regulering. Sammenlignet med nogle genbaserede metoder som ribosome engineering, promoter engineering, regulering af transkriptionsfaktorer osv. har ikke-retningsbestemte aktiveringsstrategier deres egne fordele og begr\u00e6nsninger (se tabel 4). I de senere \u00e5r er der blevet udviklet nogle nye og banebrydende metoder, s\u00e5som mikrofluidiske platforme, kombinationen af mikrofermentering og metaboliske modeller i genomskala, kombinationen af biogene r\u00f8r og genomik, HiTE'er osv. som spiller en stor rolle i stimuleringen af tavse genklynger. Kombinationen af ikke-m\u00e5lrettede aktiveringsstrategier med metabolit-fingeraftryksanalyse har vist sig at give betydelige resultater i udvindingen af sekund\u00e6re metabolitter.<\/p>","protected":false},"excerpt":{"rendered":"<p>Research progress on mining active secondary metabolites of Streptomyces using non directed activation silencing gene clusters Microbial secondary metabolites are a class of structurally diverse, functionally complex, and biologically active substances that play an important role in drug research and development. As of now, approximately 300000 compounds have been identified from microorganisms, with over 60% [&hellip;]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Research progress on mining active secondary metabolites of Streptomyces using non directed activation silencing gene clusters - China Chemical Manufacturer<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/longchangextracts.com\/da\/streptomyces-using-non-directed-activation-silencing-gene-clusters\/\" \/>\n<meta property=\"og:locale\" content=\"da_DK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Research progress on mining active secondary metabolites of Streptomyces using non directed activation silencing gene clusters - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Research progress on mining active secondary metabolites of Streptomyces using non directed activation silencing gene clusters Microbial secondary metabolites are a class of structurally diverse, functionally complex, and biologically active substances that play an important role in drug research and development. 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