Engineering Yarrowia lipolytica as a Chassis for De Novo Synthesis of Five Aromatic-Derived Natural Products and Chemicals

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dc.contributor.authorGu, Yang
dc.contributor.authorMa, Jingbo
dc.contributor.authorZhu, Yonglian
dc.contributor.authorDing, Xinyu
dc.contributor.authorXu, Peng
dc.date.accessioned2020-08-17T16:31:51Z
dc.date.available2020-08-17T16:31:51Z
dc.date.issued2020-07-10
dc.description.abstractYarrowia lipolytica is a novel microbial chassis to upgrade renewable low-cost carbon feedstocks to high-value commodity chemicals and natural products. In this work, we systematically characterized and removed the rate-limiting steps of the shikimate pathway and achieved de novo synthesis of five aromatic chemicals in Y. lipolytica. We determined that eliminating amino acids formation and engineering feedback-insensitive DAHP synthases are critical steps to mitigate precursor competition and relieve the feedback regulation of the shikimate pathway. Further overexpression of heterologous phosphoketolase and deletion of pyruvate kinase provided a sustained metabolic driving force that channels E4P (erythrose 4-phosphate) and PEP (phosphoenolpyruvate) precursors through the shikimate pathway. Precursor competing pathways and byproduct formation pathways were also blocked by inactivating chromosomal genes. To demonstrate the utility of our engineered chassis strain, three natural products, 2-phenylethanol (2-PE), p-coumaric acid, and violacein, which were derived from phenylalanine, tyrosine, and tryptophan, respectively, were chosen to test the chassis performance. We obtained 2426.22 ± 48.33 mg/L of 2-PE, 593.53 ± 28.75 mg/L of p-coumaric acid, 12.67 ± 2.23 mg/L of resveratrol, 366.30 ± 28.99 mg/L of violacein, and 55.12 ± 2.81 mg/L of deoxyviolacein from glucose in a shake flask. The 2-PE production represents a 286-fold increase over the initial strain (8.48 ± 0.50 mg/L). Specifically, we obtained the highest 2-PE, violacein, and deoxyviolacein titer ever reported from the de novo shikimate pathway in yeast. These results set up a new stage of engineering Y. lipolytica as a sustainable biorefinery chassis strain for de novo synthesis of aromatic compounds with economic values.en_US
dc.description.sponsorshipWe would like to acknowledge Bill & Melinda Gates Foundation (grant number OPP1188443) and National Science Foundation (CBET-1805139) for financially supporting this project. The authors would also like to acknowledge the Department of Chemical, Biochemical and Environmental Engineering at University of Maryland Baltimore County for funding support. YG would like to thank the China Scholarship Council for funding support.en_US
dc.description.urihttps://pubs.acs.org/doi/10.1021/acssynbio.0c00185en_US
dc.format.extent11 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/m2apnw-0kop
dc.identifier.citationYang Gu , Jingbo Ma, Yonglian Zhu, Xinyu Ding, and Peng Xu, Engineering Yarrowia lipolytica as a Chassis for De Novo Synthesis of Five Aromatic-Derived Natural Products and Chemicals, ACS Synthetic Biology Article ASAP DOI: 10.1021/acssynbio.0c00185en_US
dc.identifier.urihttps://doi.org/10.1021/acssynbio.0c00185
dc.identifier.urihttp://hdl.handle.net/11603/19439
dc.language.isoen_USen_US
dc.publisherACS Publicationsen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemical, Biochemical & Environmental Engineering Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.titleEngineering Yarrowia lipolytica as a Chassis for De Novo Synthesis of Five Aromatic-Derived Natural Products and Chemicalsen_US
dc.typeTexten_US

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