Engineering Yarrowia lipolytica for the biosynthesis of geraniol
Geraniol is a monoterpene with wide applications in the food, cosmetics, and pharmaceutical industries. Microbial production has largely used model organisms lacking favorable properties for monoterpene production. In this work, we produced geraniol in metabolically engineered Yarrowia lipolytica. F...
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Format: | Article |
Language: | English |
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Elsevier
2023-12-01
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Series: | Metabolic Engineering Communications |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2214030123000111 |
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author | Ayushi Agrawal Zhiliang Yang Mark Blenner |
author_facet | Ayushi Agrawal Zhiliang Yang Mark Blenner |
author_sort | Ayushi Agrawal |
collection | DOAJ |
description | Geraniol is a monoterpene with wide applications in the food, cosmetics, and pharmaceutical industries. Microbial production has largely used model organisms lacking favorable properties for monoterpene production. In this work, we produced geraniol in metabolically engineered Yarrowia lipolytica. First, two plant-derived geraniol synthases (GES) from Catharanthus roseus (Cr) and Valeriana officinalis (Vo) were tested based on previous reports of activity. Both wild type and truncated mutants of GES (without signal peptide targeting chloroplast) were examined by co-expressing with MVA pathway enzymes tHMG1 and IDI1. Truncated CrGES (tCrGES) produced the most geraniol and thus was used for further experimentation. The initial strain was obtained by overexpression of the truncated HMG1, IDI and tCrGES. The acetyl-CoA precursor pool was enhanced by overexpressing mevalonate pathway genes such as ERG10, HMGS or MVK, PMK. The final strain overexpressing 3 copies of tCrGES and single copies of ERG10, HMGS, tHMG1, IDI produced approximately 1 g/L in shake-flask fermentation. This is the first demonstration of geraniol production in Yarrowia lipolytica and the highest de novo titer reported to date in yeast. |
first_indexed | 2024-03-09T03:11:25Z |
format | Article |
id | doaj.art-d5cf8a74012440d8837404cae8faa856 |
institution | Directory Open Access Journal |
issn | 2214-0301 |
language | English |
last_indexed | 2024-03-09T03:11:25Z |
publishDate | 2023-12-01 |
publisher | Elsevier |
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series | Metabolic Engineering Communications |
spelling | doaj.art-d5cf8a74012440d8837404cae8faa8562023-12-04T05:21:52ZengElsevierMetabolic Engineering Communications2214-03012023-12-0117e00228Engineering Yarrowia lipolytica for the biosynthesis of geraniolAyushi Agrawal0Zhiliang Yang1Mark Blenner2Department of Chemical and Biomolecular Engineering, 590 Avenue 1743, University of Delaware, Newark, DE, 19713, USADepartment of Chemical and Biomolecular Engineering, Clemson University, 206 S. Palmetto Blvd., Clemson, SC, 29634, USADepartment of Chemical and Biomolecular Engineering, 590 Avenue 1743, University of Delaware, Newark, DE, 19713, USA; Department of Chemical and Biomolecular Engineering, Clemson University, 206 S. Palmetto Blvd., Clemson, SC, 29634, USA; Corresponding author. Department of Chemical and Biomolecular Engineering, 590 Avenue 1743, University of Delaware, Newark, DE, 19713, USA.Geraniol is a monoterpene with wide applications in the food, cosmetics, and pharmaceutical industries. Microbial production has largely used model organisms lacking favorable properties for monoterpene production. In this work, we produced geraniol in metabolically engineered Yarrowia lipolytica. First, two plant-derived geraniol synthases (GES) from Catharanthus roseus (Cr) and Valeriana officinalis (Vo) were tested based on previous reports of activity. Both wild type and truncated mutants of GES (without signal peptide targeting chloroplast) were examined by co-expressing with MVA pathway enzymes tHMG1 and IDI1. Truncated CrGES (tCrGES) produced the most geraniol and thus was used for further experimentation. The initial strain was obtained by overexpression of the truncated HMG1, IDI and tCrGES. The acetyl-CoA precursor pool was enhanced by overexpressing mevalonate pathway genes such as ERG10, HMGS or MVK, PMK. The final strain overexpressing 3 copies of tCrGES and single copies of ERG10, HMGS, tHMG1, IDI produced approximately 1 g/L in shake-flask fermentation. This is the first demonstration of geraniol production in Yarrowia lipolytica and the highest de novo titer reported to date in yeast.http://www.sciencedirect.com/science/article/pii/S2214030123000111GeraniolYarrowia lipolyticaMonoterpeneMetabolic engineering |
spellingShingle | Ayushi Agrawal Zhiliang Yang Mark Blenner Engineering Yarrowia lipolytica for the biosynthesis of geraniol Metabolic Engineering Communications Geraniol Yarrowia lipolytica Monoterpene Metabolic engineering |
title | Engineering Yarrowia lipolytica for the biosynthesis of geraniol |
title_full | Engineering Yarrowia lipolytica for the biosynthesis of geraniol |
title_fullStr | Engineering Yarrowia lipolytica for the biosynthesis of geraniol |
title_full_unstemmed | Engineering Yarrowia lipolytica for the biosynthesis of geraniol |
title_short | Engineering Yarrowia lipolytica for the biosynthesis of geraniol |
title_sort | engineering yarrowia lipolytica for the biosynthesis of geraniol |
topic | Geraniol Yarrowia lipolytica Monoterpene Metabolic engineering |
url | http://www.sciencedirect.com/science/article/pii/S2214030123000111 |
work_keys_str_mv | AT ayushiagrawal engineeringyarrowialipolyticaforthebiosynthesisofgeraniol AT zhiliangyang engineeringyarrowialipolyticaforthebiosynthesisofgeraniol AT markblenner engineeringyarrowialipolyticaforthebiosynthesisofgeraniol |