Rational engineering of Kluyveromyces marxianus to create a chassis for the production of aromatic products

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dc.contributor.authorRajkumar, Arun S.
dc.contributor.authorMorrissey, John P.
dc.contributor.funderHorizon 2020en
dc.date.accessioned2022-03-14T15:22:07Z
dc.date.available2022-03-14T15:22:07Z
dc.date.issued2020-11
dc.date.updated2022-03-14T14:51:09Z
dc.description.abstractBackground: The yeast Kluyveromyces marxianus offers unique potential for industrial biotechnology because of useful features like rapid growth, thermotolerance and a wide substrate range. As an emerging alternative platform, K. marxianus requires the development and validation of metabolic engineering strategies to best utilise its metabolism as a basis for bio-based production. Results: To illustrate the synthetic biology strategies to be followed and showcase its potential, we describe a comprehensive approach to rationally engineer a metabolic pathway in K. marxianus. We use the phenylalanine biosynthetic pathway both as a prototype and because phenylalanine is a precursor for commercially valuable secondary metabolites. First, we modify and overexpress the pathway to be resistant to feedback inhibition so as to overproduce phenylalanine de novo from synthetic minimal medium. Second, we assess native and heterologous means to increase precursor supply to the biosynthetic pathway. Finally, we eliminate branch points and competing reactions in the pathway and rebalance precursors to redirect metabolic flux to a specific product, 2-phenylethanol (2-PE). As a result, we are able to construct robust strains capable of producing over 800 mg L-1 2-PE from minimal medium. Conclusions: The strains we constructed are a promising platform for the production of aromatic amino acid-based biochemicals, and our results illustrate challenges with attempting to combine individually beneficial modifications in an integrated platform.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid207en
dc.identifier.citationRajkumar, A. S. and Morrissey, J. P. (2020) 'Rational engineering of Kluyveromyces marxianus to create a chassis for the production of aromatic products', Microbial Cell Factories, 19, 207 (19pp). doi: 10.1186/s12934-020-01461-7en
dc.identifier.doi10.1186/s12934-020-01461-7en
dc.identifier.endpage19en
dc.identifier.issn1475-2859
dc.identifier.journaltitleMicrobial Cell Factoriesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/12913
dc.identifier.volume19en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::RIA/720824/EU/Model-Based Construction And Optimisation Of Versatile Chassis Yeast Strains For Production Of Valuable Lipid And Aromatic Compounds/CHASSYen
dc.rights© The Author(s), 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativeco mmons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectAmino-acid biosynthesisen
dc.subjectP-coumaric aciden
dc.subjectSaccharomyces-cerevisiaeen
dc.subjectYeasten
dc.subjectPyruvateen
dc.subjectPathwayen
dc.subjectGlucoseen
dc.subjectProteinen
dc.subjectGeneen
dc.subject2-phenylethanolen
dc.subjectAromatic amino aciden
dc.subjectShikimate pathwayen
dc.subjectPentose phosphate pathwayen
dc.subjectPhosphoketolaseen
dc.subjectPEP synthaseen
dc.titleRational engineering of Kluyveromyces marxianus to create a chassis for the production of aromatic productsen
dc.typeArticle (peer-reviewed)en
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