Zz Newly Risen From Yeast_ THC - The New York Times

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Zz Newly Risen From Yeast_ THC - The New York Times

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    SCIENCE

    NewlyRisenFromYeast:THCByROXANNEKHAMSI SEPT.14,2015

    InAugust,researchersannouncedtheyhadgeneticallyengineeredyeasttoproducethepowerfulpainkillerhydrocodone.Nowcomestheperhapsinevitablesequel:Scientistshavecreatedyeaststhatcanmakeimportantconstituentsofmarijuana,includingthemainpsychoactivecompound,tetrahydrocannabinol,orTHC.

    SyntheticversionsofTHCareavailableinpillformunderbrandnameslikeMarinolandCesamettheyaregenerallyusedtotreatnausea,vomitingandlossofappetitecausedbyH.I.V.infectionorcancerchemotherapy.GeneticallymodifiedyeastcouldmakeTHCinacheaperandmorestreamlinedwaythantraditionalchemicalsynthesis.

    Usingyeastcouldalsoshedlightontheclinicalusefulnessofcannabisderivedcompounds.Marijuanaisincreasinglyembracedasmedicine,yetthereislimitedevidencethatitiseffectiveagainstmanyoftheconditionsforwhichitisprescribed.Researchershopingtoseparatefactfromwishfulthinkingwillneedmuchbetteraccesstomarijuanasuniqueconstituents.Modifiedyeastmayprovidethem.

    Thisissomethingthatcouldliterallychangethelivesofmillionsofpeople,saidKevinChen,thechiefexecutiveofHyasynthBio,acompanyworkingtocreateyeaststhatproduceTHCandcannabidiol,anothermarijuanacompoundofmedicinalinterest.

    InapaperpublishedthismonthinthejournalBiotechnologyLetters,

  • biochemistsattheTechnicalUniversityofDortmundinGermanyreportedthattheyhadengineeredastrainofyeastthatproducesTHC.Theyalsohaveunpublisheddatatoshowtheysucceededincreatingayeaststrainthatcanmakecannabidiol.

    Bothyeastsrelyonsocalledprecursormoleculesnotsimplesugars,whichwouldbeidealandcanproduceonlysmallamountsofTHCandcannabidiol.ButOliverKayser,abiochemistattheuniversity,hopesthathecaneventuallyengineertheyeasttoreplicatethefullTHCproductionpathwayandhasteamedwithTHCPharmofFrankfurttotrytoscaletheprocessesforindustrialproduction.

    Europeanregulators,hesaid,areeagerforawaytocreateasteadysupplyofTHCandothercannabinoidswithoutactuallycultivatingmarijuana.Theyareinfearthattheseplantswillbegrownandwillsupportsomeillegalfarming,Dr.Kaysersaid.

    Theideaisnotnew.EffortstogetyeasttosynthesizeTHCdatebackatleasteightyears,whenJapanesescientistspublishedastudydetailinghowtheyinsertedageneintoPichiapastoristhatcoaxedittosecreteanenzymenecessarytoproduceTHC.

    ButtheresearchersdidnotknowalloftheenzymesusedbythemarijuanaplanttomakeTHC.Overthelastdecade,withthehelpofcheaperandfasterDNAanalysistools,theyhavefoundthekeygenes.

    Dr.JonathanPage,anadjunctprofessorattheUniversityofBritishColumbiawhohelpedinthesesequencingefforts,setupacompanycalledAnandiaLaboratoriesinparttoreproducesubstancesincannabiswithyeast.HiscompanyandHyasynthBio,Mr.Chensfirm,awaitapprovalfromtheCanadiangovernmenttoengineertheirownTHCproducingyeaststrains.

    Dr.Page,whoholdspatentapplicationsforseveralofthegenesintheTHCsynthesispathway,saidheanticipatedreceivingthegoaheadfromtheauthoritiesthisyear.Otherbiotechfirmsareexploringtheidea,

  • includingAmyris,abiotechcompanyinEmeryville,Calif.,thathasusedyeasttochurnoutproductsrangingfromtheantimalarialdrugartemisinintoapatchoulifragrance.

    Butallthisnewbiotechnologyfacestoughcompetitionfromthecannabisplantitself.MarijuanahasbeensocarefullybredforsomanyyearsthatithasbecomearemarkablyefficientproducerofTHC.Somestrainscontainmorethan30percentTHCcontentbydryweight.

    Rightnow,wehaveaplantthatisessentiallytheFerrarioftheplantworldwhenitcomestoproducingthechemicalofinterest,Dr.Pagesaid.Cannabisishardtobeat.

    Forthisreason,heandhiscompanyalsohopetouseyeasttomakechemicalsfoundintraceamountsincannabisthathaveshownearlypromiseaspotentialmedicines.Theseincludecannabidivarin,whichhaspreventedseizuresinpreliminaryrodentstudies,andtetrahydrocannabivarin,whichmaybeanantiinflammatory,amongotheruses.

    InlateJune,Dr.NoraVolkow,thedirectoroftheNationalInstituteonDrugAbuse,spokeatahearingbeforeaSenatecaucusaboutthepotentialbenefitsofcannabidiol,whichisbeingstudiedfordisorderssuchasepilepsy.Somescientistsbelieveitisthesubstancethatshouldbeprioritizedforproductioninyeast.

    IwonderwhyanybodyshouldtrytogetyeasttoproduceTHC,saidRaphaelMechoulam,whowithacolleagueidentifiedTHCastheactivesubstanceincannabisin1964.Cannabidiolproductionisadifferentstory.Itsproductionfromplantsisabitcomplicated.And,headded,demandforitisgrowing.

    Still,itsanenormouschallengetomodifyyeasttosynthesizeTHCorcannabidiolfromrawmaterialslikesugarthecurrentstrainsinDr.Kayserslaboratoryarecapableofonlythefinalstageofthesynthesis.Ultimately,biochemistsmayneedtoinsertmorethanadozengenesinto

  • theyeast.

    Atonelevel,youcansaythatnothinglimitsyoubutyourimagination,saidDr.PamelaSilver,aprofessorofsystemsbiologyatHarvardMedicalSchool.But,sheadded,Thisisactuallyreallyhard.

    Oneproposalthatremainsoffthetable:designingyeasttohelpbrewTHCinfusedbeer.

    Peoplekeepaskingaboutit,Mr.Chensaid.Buttheresbiggerpotentialtherethanjustmakingabeer.

    AversionofthisarticleappearsinprintonSeptember15,2015,onpageD3oftheNewYorkeditionwiththeheadline:NewlyRisenFromYeast:THC.

    2015TheNewYorkTimesCompany


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