Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus
Lovastatin is widely prescribed to reduce elevated levels of cholesterol and prevent heart-related diseases. Cultivation of Aspergillus terreus (ATCC 20542) with carbohydrates or low-value feedstocks such as glycerol produces lovastatin as a secondary metabolite and (+)-geodin as a by-product. An A....
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Elsevier BV
2019
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Online Access: | http://psasir.upm.edu.my/id/eprint/80185/1/Improved%20lovastatin%20production%20by%20inhibiting%20%28%2B%29-geodin%20biosynthesis%20in%20aspergillus%20terreus.pdf http://psasir.upm.edu.my/id/eprint/80185/ https://pubmed.ncbi.nlm.nih.gov/30995533/ |
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my.upm.eprints.801852020-10-01T07:29:49Z http://psasir.upm.edu.my/id/eprint/80185/ Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus Hasan, Hanan Abd Rahim, Muhamad Hafiz Campbell, Leona Carter, Dee Montoya, Alejandro Abbas, Ali Lovastatin is widely prescribed to reduce elevated levels of cholesterol and prevent heart-related diseases. Cultivation of Aspergillus terreus (ATCC 20542) with carbohydrates or low-value feedstocks such as glycerol produces lovastatin as a secondary metabolite and (+)-geodin as a by-product. An A. terreus mutant strain was developed (gedCΔ) with a disrupted (+)-geodin biosynthesis pathway. The gedCΔ mutant was created by inserting the antibiotic marker hygromycin B (hyg) within the gedC gene that encodes emodin anthrone polyketide synthase (PKS), a primary gene responsible for initiating (+)-geodin biosynthesis. The effects of emodin anthrone PKS gene disruption on (+)-geodin and lovastatin biosynthesis and the production of the precursors acetyl-CoA and malonyl-CoA were investigated with cultures based on glycerol alone and in combination with lactose. The gedCΔ strain showed improved lovastatin production, particularly when cultivated on the glycerol-lactose mixture, increasing lovastatin production by 80% (113 mg/L) while simultaneously inhibiting (+)-geodin biosynthesis compared to the wild-type strain. This study thus shows that suppression of the (+)-geodin pathway increases lovastatin yield and demonstrates a practical approach of manipulating carbon flux by modulating enzyme activity. Elsevier BV 2019 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/80185/1/Improved%20lovastatin%20production%20by%20inhibiting%20%28%2B%29-geodin%20biosynthesis%20in%20aspergillus%20terreus.pdf Hasan, Hanan and Abd Rahim, Muhamad Hafiz and Campbell, Leona and Carter, Dee and Montoya, Alejandro and Abbas, Ali (2019) Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus. New Biotechnology, 52. pp. 19-24. ISSN 1871-6784; ESSN: 1876-4347 https://pubmed.ncbi.nlm.nih.gov/30995533/ 10.1016/j.nbt.2019.04.003 |
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Lovastatin is widely prescribed to reduce elevated levels of cholesterol and prevent heart-related diseases. Cultivation of Aspergillus terreus (ATCC 20542) with carbohydrates or low-value feedstocks such as glycerol produces lovastatin as a secondary metabolite and (+)-geodin as a by-product. An A. terreus mutant strain was developed (gedCΔ) with a disrupted (+)-geodin biosynthesis pathway. The gedCΔ mutant was created by inserting the antibiotic marker hygromycin B (hyg) within the gedC gene that encodes emodin anthrone polyketide synthase (PKS), a primary gene responsible for initiating (+)-geodin biosynthesis. The effects of emodin anthrone PKS gene disruption on (+)-geodin and lovastatin biosynthesis and the production of the precursors acetyl-CoA and malonyl-CoA were investigated with cultures based on glycerol alone and in combination with lactose. The gedCΔ strain showed improved lovastatin production, particularly when cultivated on the glycerol-lactose mixture, increasing lovastatin production by 80% (113 mg/L) while simultaneously inhibiting (+)-geodin biosynthesis compared to the wild-type strain. This study thus shows that suppression of the (+)-geodin pathway increases lovastatin yield and demonstrates a practical approach of manipulating carbon flux by modulating enzyme activity. |
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Hasan, Hanan Abd Rahim, Muhamad Hafiz Campbell, Leona Carter, Dee Montoya, Alejandro Abbas, Ali |
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Hasan, Hanan Abd Rahim, Muhamad Hafiz Campbell, Leona Carter, Dee Montoya, Alejandro Abbas, Ali Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus |
author_facet |
Hasan, Hanan Abd Rahim, Muhamad Hafiz Campbell, Leona Carter, Dee Montoya, Alejandro Abbas, Ali |
author_sort |
Hasan, Hanan |
title |
Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus |
title_short |
Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus |
title_full |
Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus |
title_fullStr |
Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus |
title_full_unstemmed |
Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus |
title_sort |
improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus |
publisher |
Elsevier BV |
publishDate |
2019 |
url |
http://psasir.upm.edu.my/id/eprint/80185/1/Improved%20lovastatin%20production%20by%20inhibiting%20%28%2B%29-geodin%20biosynthesis%20in%20aspergillus%20terreus.pdf http://psasir.upm.edu.my/id/eprint/80185/ https://pubmed.ncbi.nlm.nih.gov/30995533/ |
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13.18916 |