Engineering Yarrowia lipolytica for Campesterol Overproduction.
Campesterol is an important precursor for many sterol drugs, e.g. progesterone and hydrocortisone. In order to produce campesterol in Yarrowia lipolytica, C-22 desaturase encoding gene ERG5 was disrupted and the heterologous 7-dehydrocholesterol reductase (DHCR7) encoding gene was constitutively exp...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4709189?pdf=render |
| _version_ | 1818135367702806528 |
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| author | Hao-Xing Du Wen-Hai Xiao Ying Wang Xiao Zhou Yu Zhang Duo Liu Ying-Jin Yuan |
| author_facet | Hao-Xing Du Wen-Hai Xiao Ying Wang Xiao Zhou Yu Zhang Duo Liu Ying-Jin Yuan |
| author_sort | Hao-Xing Du |
| collection | DOAJ |
| description | Campesterol is an important precursor for many sterol drugs, e.g. progesterone and hydrocortisone. In order to produce campesterol in Yarrowia lipolytica, C-22 desaturase encoding gene ERG5 was disrupted and the heterologous 7-dehydrocholesterol reductase (DHCR7) encoding gene was constitutively expressed. The codon-optimized DHCR7 from Rallus norvegicus, Oryza saliva and Xenapus laevis were explored and the strain with the gene DHCR7 from X. laevis achieved the highest titer of campesterol due to D409 in substrate binding sites. In presence of glucose as the carbon source, higher biomass conversion yield and product yield were achieved in shake flask compared to that using glycerol and sunflower seed oil. Nevertheless, better cell growth rate was observed in medium with sunflower seed oil as the sole carbon source. Through high cell density fed-batch fermentation under carbon source restriction strategy, a titer of 453±24.7 mg/L campesterol was achieved with sunflower seed oil as the carbon source, which is the highest reported microbial titer known. Our study has greatly enhanced campesterol accumulation in Y. lipolytica, providing new insight into producing complex and desired molecules in microbes. |
| first_indexed | 2024-12-11T09:23:23Z |
| format | Article |
| id | doaj.art-0126cae69784480eb30fe18c3e42c570 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:23:23Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0126cae69784480eb30fe18c3e42c5702022-12-22T01:13:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014677310.1371/journal.pone.0146773Engineering Yarrowia lipolytica for Campesterol Overproduction.Hao-Xing DuWen-Hai XiaoYing WangXiao ZhouYu ZhangDuo LiuYing-Jin YuanCampesterol is an important precursor for many sterol drugs, e.g. progesterone and hydrocortisone. In order to produce campesterol in Yarrowia lipolytica, C-22 desaturase encoding gene ERG5 was disrupted and the heterologous 7-dehydrocholesterol reductase (DHCR7) encoding gene was constitutively expressed. The codon-optimized DHCR7 from Rallus norvegicus, Oryza saliva and Xenapus laevis were explored and the strain with the gene DHCR7 from X. laevis achieved the highest titer of campesterol due to D409 in substrate binding sites. In presence of glucose as the carbon source, higher biomass conversion yield and product yield were achieved in shake flask compared to that using glycerol and sunflower seed oil. Nevertheless, better cell growth rate was observed in medium with sunflower seed oil as the sole carbon source. Through high cell density fed-batch fermentation under carbon source restriction strategy, a titer of 453±24.7 mg/L campesterol was achieved with sunflower seed oil as the carbon source, which is the highest reported microbial titer known. Our study has greatly enhanced campesterol accumulation in Y. lipolytica, providing new insight into producing complex and desired molecules in microbes.http://europepmc.org/articles/PMC4709189?pdf=render |
| spellingShingle | Hao-Xing Du Wen-Hai Xiao Ying Wang Xiao Zhou Yu Zhang Duo Liu Ying-Jin Yuan Engineering Yarrowia lipolytica for Campesterol Overproduction. PLoS ONE |
| title | Engineering Yarrowia lipolytica for Campesterol Overproduction. |
| title_full | Engineering Yarrowia lipolytica for Campesterol Overproduction. |
| title_fullStr | Engineering Yarrowia lipolytica for Campesterol Overproduction. |
| title_full_unstemmed | Engineering Yarrowia lipolytica for Campesterol Overproduction. |
| title_short | Engineering Yarrowia lipolytica for Campesterol Overproduction. |
| title_sort | engineering yarrowia lipolytica for campesterol overproduction |
| url | http://europepmc.org/articles/PMC4709189?pdf=render |
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