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Your search keyword '"Mukhopadhyay, Aindrila"' showing total 11 results
Start Over Author "Mukhopadhyay, Aindrila" Journal metabolic engineering
11 results on '"Mukhopadhyay, Aindrila"'

6. Machine learning for metabolic engineering: A review

Author

Lawson, Christopher E., Martí, Jose Manuel, Radivojevic, Tijana, Jonnalagadda, Sai Vamshi R., Gentz, Reinhard, Hillson, Nathan J., Peisert, Sean, Kim, Joonhoon, Simmons, Blake A., Petzold, Christopher J., Singer, Steven W., Mukhopadhyay, Aindrila, Tanjore, Deepti, Dunn, Joshua G., and Garcia Martin, Hector

Published
2021
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11. Engineering high-level production of fatty alcohols by Saccharomyces cerevisiae from lignocellulosic feedstocks.

Author

d'Espaux L, Ghosh A, Runguphan W, Wehrs M, Xu F, Konzock O, Dev I, Nhan M, Gin J, Reider Apel A, Petzold CJ, Singh S, Simmons BA, Mukhopadhyay A, García Martín H, and Keasling JD

Subjects
Alcohol Dehydrogenase genetics, Alcohol Dehydrogenase metabolism, Aldehyde Oxidoreductases genetics, Aldehyde Oxidoreductases metabolism, Animals, Diacylglycerol O-Acyltransferase genetics, Diacylglycerol O-Acyltransferase metabolism, Gene Deletion, Mice, Recombinant Proteins genetics, Recombinant Proteins metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Stearoyl-CoA Desaturase genetics, Stearoyl-CoA Desaturase metabolism, Fatty Alcohols metabolism, Lignin metabolism, Metabolic Engineering, Saccharomyces cerevisiae metabolism
Abstract

Fatty alcohols in the C12-C18 range are used in personal care products, lubricants, and potentially biofuels. These compounds can be produced from the fatty acid pathway by a fatty acid reductase (FAR), yet yields from the preferred industrial host Saccharomyces cerevisiae remain under 2% of the theoretical maximum from glucose. Here we improved titer and yield of fatty alcohols using an approach involving quantitative analysis of protein levels and metabolic flux, engineering enzyme level and localization, pull-push-block engineering of carbon flux, and cofactor balancing. We compared four heterologous FARs, finding highest activity and endoplasmic reticulum localization from a Mus musculus FAR. After screening an additional twenty-one single-gene edits, we identified increasing FAR expression; deleting competing reactions encoded by DGA1, HFD1, and ADH6; overexpressing a mutant acetyl-CoA carboxylase; limiting NADPH and carbon usage by the glutamate dehydrogenase encoded by GDH1; and overexpressing the Δ9-desaturase encoded by OLE1 as successful strategies to improve titer. Our final strain produced 1.2g/L fatty alcohols in shake flasks, and 6.0g/L in fed-batch fermentation, corresponding to ~ 20% of the maximum theoretical yield from glucose, the highest titers and yields reported to date in S. cerevisiae. We further demonstrate high-level production from lignocellulosic feedstocks derived from ionic-liquid treated switchgrass and sorghum, reaching 0.7g/L in shake flasks. Altogether, our work represents progress towards efficient and renewable microbial production of fatty acid-derived products., (Published by Elsevier Inc.)

Published
2017
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