Biosensors: een cruciaal ingrediënt voor de bio-economie

Vincent
Crabbe

Onze afhankelijkheid van fossiele brandstoffen is brandend actueel, en hun impact op het klimaat is een van de grootste uitdagingen van deze eeuw. Daarom gebeurt veel onderzoek naar de productie van brandstof en plastics door micro-organismen, microscopisch kleine wezentjes zoals bacteriën en gisten, op basis van hernieuwbare grondstoffen. Ondanks enkele successen staat de transitie van onze petrochemische industrie naar een meer duurzame bio-economie op een laag pitje. Een belangrijke oorzaak hiervoor is dat deze micro-organismen drastisch gewijzigd moeten worden, waardoor hun metabolisme uit balans kan raken. Een mogelijke oplossing steunt op biosensors, die de concentratie van een specifieke molecule bínnenin de cel kunnen meten en zo over deze balans kunnen waken.

Hoewel sommige microben ons ziek kunnen maken, hebben bepaalde micro-organismen een enorm economisch potentieel: ze kunnen ingezet worden voor de productie van biobrandstoffen en chemicaliën. Gisten kunnen bijvoorbeeld de suikers uit biologische grondstoffen – zoals mais – fermenteren tot het waardevolle product ethanol. Dit proces wordt al duizenden jaren toegepast voor de productie van alcoholhoudende dranken, maar tegenwoordig wordt het merendeel van de geproduceerde ethanol gebruikt als brandstof. Zulke biobrandstoffen zijn namelijk beter voor het klimaat en verlagen onze afhankelijkheid van fossiele brandstoffen – en van de soms obscure regimes die ons hiervan bevoorraden.

Voorts wordt 12% van de aardolie die we wereldwijd oppompen gebruikt in de petrochemische industrie, onder andere voor de productie van plastics. Ook hier vormen micro-organismen een belangrijk alternatief. Zo produceren bepaalde micro-organismen biodegradeerbare plastics op basis van hernieuwbare grondstoffen. Er is echter nog veel werk aan de winkel om alle producten uit ons dagelijks leven te vervangen door een biologisch alternatief.

In deze context hechten biotechnologen bijvoorbeeld veel belang aan 3-HP (3-HydroxyPropionzuur). Deze molecule kan op basis van verscheidene hernieuwbare grondstoffen geproduceerd worden en kan makkelijk omgezet worden in een reeks chemicaliën met diverse toepassingen, goed voor een totale marktomvang van meer dan 30 miljard dollar.

Meten is weten

Eén probleem: micro-organismen produceren van nature niet voldoende 3-HP om een economisch interessant proces te ontwikkelen. En dus proberen bio-ingenieurs van over de hele wereld deze micro-organismen te verbeteren. Hierbij moeten heel wat wijzigingen aan het micro-organisme worden aangebracht. Deze ingrepen kunnen echter de balans in het metabolisme ontwrichten.

Veel wetenschappers, onder wie mijn promotors Eveline Peeters en Sophie de Buyl en ikzelf, trachten dit probleem aan te pakken aan de hand van biosensors. Zulke sensors laten toe om de concentratie van bepaalde moleculen binnenin de microbiële cel in realtime te meten.

Want meten is weten. Stel je bijvoorbeeld voor: je probeert een cake te maken … zonder weegschaal. Zo wordt het moeilijk om alle ingrediënten in de juiste verhouding toe te voegen. En als je ook tussendoor niet mag proeven van het beslag, heb je al helemaal geen idee waar je mee bezig bent.

Dat is precies de troef van biosensors: ze laten je toe om de juiste verhouding van de “ingrediënten” van het waardevolle molecule 3-HP (“de cake”) in te stellen binnenin de cel die dit produceert. Of door de concentratie van intermediaire producten op te volgen met zo’n biosensor (in “het beslag”), kan de ingenieur het proces in realtime fijnregelen, en zo de balans herstellen.

Biosensors zijn moeilijk af te regelen

Niettegenstaande hun potentieel al meermaals bewezen is in experimentele opstellingen, hebben biosensors nog niet hun weg naar de industrie gevonden. Het blijft namelijk een uitdaging om biosensors af te regelen voor een concrete toepassing. Want zoals dikwijls in de biologie, zijn ook biosensors behoorlijk complex en kan een bepaalde modificatie naast het beoogde effect ook ongewenste of zelfs averechtse effecten uitlokken. Daarom rekenen wetenschappers voor hun ontwikkeling vaak op proefondervindelijke methoden, die veel tijd en geld kosten en – ironisch genoeg – in veel plastic afval van gebruiksvoorwerpen uit het laboratorium resulteren.

Om tijd en middelen te sparen, gebruikte ik voor een groot deel van mijn masterproef een wiskundig model uit de wetenschappelijke literatuur. Dit model voorspelt het outputsignaal van de biosensor in functie van de concentratie van het doelwitmolecule – het molecule dat de biosensor waarneemt. Achter de computer bracht ik dan modificaties aan bij een fictieve biosensor en evalueerde vervolgens het voorspelde effect op de output. Zo kon ik een heleboel experimenten simuleren die in realiteit jaren in beslag zouden nemen.

Toch kwamen niet alle simulaties overeen met eerdere experimenten uit de wetenschappelijke literatuur. Dit suggereert dat het model een belangrijk biologisch aspect over het hoofd ziet. Dat lijkt jammer, maar toch blijft dit model aantrekkelijk door zijn eenvoud. Mijn scriptie legde de basis om in te toekomst de grenzen aan de toepasbaarheid van dit model vast te leggen.

In het tweede deel van mijn masterproef bestudeerde ik biosensors die de concentratie van β-alanine, een intermediaire molecule voor de productie van 3-HP, meten in het laboratorium. Of je zou kunnen zeggen dat je met deze biosensors “van het beslag kan proeven”. De ontwikkelde biosensors werden uitgebreid gekarakteriseerd en kunnen in de toekomst geselecteerd worden voor diverse toepassingen.

Conclusie

Onze tweeledige aanpak – wiskundig modelleren in combinatie met praktisch werk in het laboratorium – is redelijk zeldzaam maar zeer nuttig. Het modelleren laat toe om efficiënt biosensor-ontwerpen te testen en de meest interessante parameters uit te kiezen. Deze theorie moet uiteraard omgezet worden in praktijk, en daarom ontwikkelde ik verschillende biosensors in de context van een belangrijke toepassing: de productie van het waardevolle molecule 3-HP. Maar de vertaling van deze biosensors naar de industrie zal nog jaren duren, want dat is geen piece of cake

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Universiteit of Hogeschool
Vrije Universiteit Brussel
Thesis jaar
2022
Promotor(en)
Prof. Dr. ir. Eveline Peeters, Prof. Dr. Sophie de Buyl
Kernwoorden