Development of hypertolerant strain of Yarrowia lipolytica accumulating succinic acid using high levels of acetate

dc.contributor.authorNarisetty, Vivek
dc.contributor.authorPrabhu, Ashish A.
dc.contributor.authorBommareddy, Rajesh Reddy
dc.contributor.authorCox, Rylan
dc.contributor.authorAgrawal, Deepti
dc.contributor.authorMisra, Ashish
dc.contributor.authorAli Haider, M.
dc.contributor.authorBhatnagar, Amit
dc.contributor.authorPandey, Ashok
dc.contributor.authorKumar, Vinod
dc.date.accessioned2022-08-23T09:02:51Z
dc.date.available2022-08-23T09:02:51Z
dc.date.issued2022-08-09
dc.description.abstractAcetate is emerging as a promising feedstock for biorefineries as it can serve as an alternate carbon source for microbial cell factories. In this study, we expressed acetyl-CoA synthase in Yarrowia lipolytica PSA02004PP, and the recombinant strain grew on acetate as the sole carbon source and accumulated succinic acid or succinate (SA). Unlike traditional feedstocks, acetate is a toxic substrate for microorganisms; therefore, the recombinant strain was further subjected to adaptive laboratory evolution to alleviate toxicity and improve tolerance against acetate. At high acetate concentrations, the adapted strain Y. lipolytica ACS 5.0 grew rapidly and accumulated lipids and SA. Bioreactor cultivation of ACS 5.0 with 22.5 g/L acetate in a batch mode resulted in a maximum cell OD600 of 9.2, with lipid and SA accumulation being 0.84 and 5.1 g/L, respectively. However, its fed-batch cultivation yielded a cell OD600 of 23.5, SA titer of 6.5 g/L, and lipid production of 1.5 g/L with an acetate uptake rate of 0.2 g/L h, about 2.86 times higher than the parent strain. Cofermentation of acetate and glucose significantly enhanced the SA titer and lipid accumulation to 12.2 and 1.8 g/L, respectively, with marginal increment in cell growth (OD600: 26.7). Furthermore, metabolic flux analysis has drawn insights into utilizing acetate for the production of metabolites that are downstream to acetyl-CoA. To the best of our knowledge, this is the first report on SA production from acetate by Y. lipolytica and demonstrates a path for direct valorization of sugar-rich biomass hydrolysates with elevated acetate levels to SA.en_UK
dc.identifier.citationNarisetty V, Prabhu AA, Bommareddy RR, et al., (2022) Development of hypertolerant strain of Yarrowia lipolytica accumulating succinic acid using high levels of acetate. ACS Sustainable Chemistry and Engineering, Volume 10, Issue 33, August 2022, pp. 10858-10869en_UK
dc.identifier.issn2168-0485
dc.identifier.urihttps://doi.org/10.1021/acssuschemeng.2c02408
dc.identifier.urihttps://dspace.lib.cranfield.ac.uk/handle/1826/18347
dc.language.isoenen_UK
dc.publisherAmerican Chemical Societyen_UK
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectacetateen_UK
dc.subjectsuccinic aciden_UK
dc.subjectYarrowia lipolyticaen_UK
dc.subjectacetyl-CoA synthaseen_UK
dc.subjectadaptive laboratory evolutionen_UK
dc.titleDevelopment of hypertolerant strain of Yarrowia lipolytica accumulating succinic acid using high levels of acetateen_UK
dc.typeArticleen_UK

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