Heterologous Biosynthesis and Genomics-Driven Derivatization of Fungal Bioactive Sesterterpenoid Variecolin
The biosynthetic gene cluster of fungal bioactive sesterterpenoids, variecolin (1) and variecolactone (2), was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues, one of which exhibited potent anticancer activity comparable to that of 1..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
chemRxiv.org - (2023) vom: 31. Aug. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yan, Dexiu [VerfasserIn] |
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| doi: |
10.26434/chemrxiv-2021-x171c |
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XCH036655430 |
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| 520 | |a The biosynthetic gene cluster of fungal bioactive sesterterpenoids, variecolin (1) and variecolactone (2), was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues, one of which exhibited potent anticancer activity comparable to that of 1. | ||
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| 700 | 1 | |a Wan, Teng |4 aut | |
| 700 | 1 | |a Chan, Tsz Ki |4 aut | |
| 700 | 1 | |a Ahn, Dohyun |4 aut | |
| 700 | 1 | |a Cheung, Tsz Kiu |4 aut | |
| 700 | 1 | |a Chan, Ho Ching |4 aut | |
| 700 | 1 | |a Choi, Inseo |4 aut | |
| 700 | 1 | |a Ho, Pui Yi |4 aut | |
| 700 | 1 | |a Hu, Feijun |4 aut | |
| 700 | 1 | |a Kim, Yujeong |4 aut | |
| 700 | 1 | |a Lau, Hill Lam |4 aut | |
| 700 | 1 | |a Law, Ying Lo |4 aut | |
| 700 | 1 | |a Leung, Chi Seng |4 aut | |
| 700 | 1 | |a Raina, Ritvik |4 aut | |
| 700 | 1 | |a Tong, Chun Yin |4 aut | |
| 700 | 1 | |a Wong, Kai Kap |4 aut | |
| 700 | 1 | |a Yim, Wing Lam |4 aut | |
| 700 | 1 | |a Babak, Maria V. |4 aut | |
| 700 | 1 | |a Kong, Richard Y. C. |4 aut | |
| 700 | 1 | |a Matsuda, Yudai |0 (orcid)0000-0001-5650-4732 |4 aut | |
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