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Candida CYP52: Alkane and fatty acid metabolism. / Claire Louise Price

Swansea University Author: Claire Louise Price

Abstract

Cytochromes P450 are a superfamily of haem-thiolate proteins found in all kingdoms of life. To date 11294 enzymes have been identified and have been shown to be involved in the metabolism of a wide variety of substrates, including hydrocarbons and xenobiotics. In yeast and fungi the hydroxylation of...

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Published: 2012
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42696
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first_indexed 2018-08-02T18:55:19Z
last_indexed 2019-10-21T16:48:17Z
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spelling 2018-08-29T15:07:30.1324187 v2 42696 2018-08-02 Candida CYP52: Alkane and fatty acid metabolism. 9d0bc073d4ff9451a35ee7be22ef6ed1 NULL Claire Louise Price Claire Louise Price true true 2018-08-02 Cytochromes P450 are a superfamily of haem-thiolate proteins found in all kingdoms of life. To date 11294 enzymes have been identified and have been shown to be involved in the metabolism of a wide variety of substrates, including hydrocarbons and xenobiotics. In yeast and fungi the hydroxylation of alkanes is associated with a family of cytochromes P450 enzymes known as CYP52s. These enzymes are involved in the terminal hydroxylation of long-chain alkanes resulting in the production of alcohols, which can be further converted to form fatty acids and diacids. In vivo such hydrocarbons can be subjected to beta-oxidation for use in growth. Alternatively, the products formed by CYP52 catalysed hydroxylation in vitro can be used in biotechnological applications. They can be used as platform chemicals in the production of a number of industrial products, including plastics, fragrances and antibiotics. The p-oxidation of fatty acids has been less well documented for Candida albicans than for other Candida species, therefore it was the aim of this study to investigate a) did cytochromes P450 exist in C. albicans that could possibly fulfil this function and b) to definitively assign function to a single cytochrome P450. Using a bioinformatic approach, five putative CYP52s were identified in C. albicans. Of these CYP52s, Alk1 was shown to have the greatest homology to the archetypal alkane-assimilating CYP52, CYP52A3 from C. maltosa. ALK1 heterologous gene expression in the brewer's yeast Saccharomyces cerevisiae allowed growth on hexadecane (C16:0) as the sole carbon source. This showed for the first time that Alk1 is involved in the hydroxylation of long-chain alkanes as normally S. cerevisiae is unable to utilise alkanes for growth. This study has also shown that Alk1 is able to interact with sterol substrates suggesting a possible role for CYP52s in sterol metabolism, which was previously unknown. E-Thesis Molecular biology. 31 12 2012 2012-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T15:07:30.1324187 2018-08-02T16:24:30.1490049 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Claire Louise Price NULL 1 0042696-02082018162514.pdf 10807465.pdf 2018-08-02T16:25:14.7500000 Output 29686524 application/pdf E-Thesis true 2018-08-02T16:25:14.7500000 false
title Candida CYP52: Alkane and fatty acid metabolism.
spellingShingle Candida CYP52: Alkane and fatty acid metabolism.
Claire Louise Price
title_short Candida CYP52: Alkane and fatty acid metabolism.
title_full Candida CYP52: Alkane and fatty acid metabolism.
title_fullStr Candida CYP52: Alkane and fatty acid metabolism.
title_full_unstemmed Candida CYP52: Alkane and fatty acid metabolism.
title_sort Candida CYP52: Alkane and fatty acid metabolism.
author_id_str_mv 9d0bc073d4ff9451a35ee7be22ef6ed1
author_id_fullname_str_mv 9d0bc073d4ff9451a35ee7be22ef6ed1_***_Claire Louise Price
author Claire Louise Price
author2 Claire Louise Price
format E-Thesis
publishDate 2012
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Cytochromes P450 are a superfamily of haem-thiolate proteins found in all kingdoms of life. To date 11294 enzymes have been identified and have been shown to be involved in the metabolism of a wide variety of substrates, including hydrocarbons and xenobiotics. In yeast and fungi the hydroxylation of alkanes is associated with a family of cytochromes P450 enzymes known as CYP52s. These enzymes are involved in the terminal hydroxylation of long-chain alkanes resulting in the production of alcohols, which can be further converted to form fatty acids and diacids. In vivo such hydrocarbons can be subjected to beta-oxidation for use in growth. Alternatively, the products formed by CYP52 catalysed hydroxylation in vitro can be used in biotechnological applications. They can be used as platform chemicals in the production of a number of industrial products, including plastics, fragrances and antibiotics. The p-oxidation of fatty acids has been less well documented for Candida albicans than for other Candida species, therefore it was the aim of this study to investigate a) did cytochromes P450 exist in C. albicans that could possibly fulfil this function and b) to definitively assign function to a single cytochrome P450. Using a bioinformatic approach, five putative CYP52s were identified in C. albicans. Of these CYP52s, Alk1 was shown to have the greatest homology to the archetypal alkane-assimilating CYP52, CYP52A3 from C. maltosa. ALK1 heterologous gene expression in the brewer's yeast Saccharomyces cerevisiae allowed growth on hexadecane (C16:0) as the sole carbon source. This showed for the first time that Alk1 is involved in the hydroxylation of long-chain alkanes as normally S. cerevisiae is unable to utilise alkanes for growth. This study has also shown that Alk1 is able to interact with sterol substrates suggesting a possible role for CYP52s in sterol metabolism, which was previously unknown.
published_date 2012-12-31T03:53:28Z
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score 11.037056

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