Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430
Coumarins, isocoumarins and their derivatives are polyketides abundant in fungal metabolites. Although they were first discovered over 50 years ago, the biosynthetic process is still not entirely understood. Herein, we report the activation of a silent nonreducing polyketide synthase that encodes a...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/21/9/490 |
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| author | Jing Yu Xiaolin Liu Chuanteng Ma Chen Li Yuhan Zhang Qian Che Guojian Zhang Tianjiao Zhu Dehai Li |
| author_facet | Jing Yu Xiaolin Liu Chuanteng Ma Chen Li Yuhan Zhang Qian Che Guojian Zhang Tianjiao Zhu Dehai Li |
| author_sort | Jing Yu |
| collection | DOAJ |
| description | Coumarins, isocoumarins and their derivatives are polyketides abundant in fungal metabolites. Although they were first discovered over 50 years ago, the biosynthetic process is still not entirely understood. Herein, we report the activation of a silent nonreducing polyketide synthase that encodes a C<sub>7</sub>-methylated isocoumarin, similanpyrone B (<b>1</b>), in a marine-derived fungus <i>Simplicillium lamellicola</i> HDN13-430 by heterologous expression. Feeding studies revealed the host enzymes can change <b>1</b> into its hydroxylated derivatives pestapyrone A (<b>2</b>). Compounds <b>1</b> and <b>2</b> showed moderate radical scavenging activities with ED<sub>50</sub> values of 67.4 µM and 104.2 µM. Our discovery fills the gap in the enzymatic elucidation of naturally occurring C<sub>7</sub>-methylated isocoumarin derivatives. |
| first_indexed | 2024-03-10T22:31:29Z |
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| id | doaj.art-d7b7d10dc52f4459b3f096e46ac2dde5 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T22:31:29Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-d7b7d10dc52f4459b3f096e46ac2dde52023-11-19T11:42:19ZengMDPI AGMarine Drugs1660-33972023-09-0121949010.3390/md21090490Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430Jing Yu0Xiaolin Liu1Chuanteng Ma2Chen Li3Yuhan Zhang4Qian Che5Guojian Zhang6Tianjiao Zhu7Dehai Li8Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaSchool of Pharmaceutical Science, Shandong University, Jinan 250100, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaCoumarins, isocoumarins and their derivatives are polyketides abundant in fungal metabolites. Although they were first discovered over 50 years ago, the biosynthetic process is still not entirely understood. Herein, we report the activation of a silent nonreducing polyketide synthase that encodes a C<sub>7</sub>-methylated isocoumarin, similanpyrone B (<b>1</b>), in a marine-derived fungus <i>Simplicillium lamellicola</i> HDN13-430 by heterologous expression. Feeding studies revealed the host enzymes can change <b>1</b> into its hydroxylated derivatives pestapyrone A (<b>2</b>). Compounds <b>1</b> and <b>2</b> showed moderate radical scavenging activities with ED<sub>50</sub> values of 67.4 µM and 104.2 µM. Our discovery fills the gap in the enzymatic elucidation of naturally occurring C<sub>7</sub>-methylated isocoumarin derivatives.https://www.mdpi.com/1660-3397/21/9/490isocoumarinsnonreducing polyketide synthase (nrPKS)<i>Simplicillium lamellicola</i>genome miningsilent gene clusters |
| spellingShingle | Jing Yu Xiaolin Liu Chuanteng Ma Chen Li Yuhan Zhang Qian Che Guojian Zhang Tianjiao Zhu Dehai Li Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430 Marine Drugs isocoumarins nonreducing polyketide synthase (nrPKS) <i>Simplicillium lamellicola</i> genome mining silent gene clusters |
| title | Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430 |
| title_full | Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430 |
| title_fullStr | Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430 |
| title_full_unstemmed | Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430 |
| title_short | Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C<sub>7</sub>-Methylated Isocoumarin in a Marine-Derived Fungus <i>Simplicillium lamellicola</i> HDN13-430 |
| title_sort | activation of a silent polyketide synthase slpks4 encoding the c sub 7 sub methylated isocoumarin in a marine derived fungus i simplicillium lamellicola i hdn13 430 |
| topic | isocoumarins nonreducing polyketide synthase (nrPKS) <i>Simplicillium lamellicola</i> genome mining silent gene clusters |
| url | https://www.mdpi.com/1660-3397/21/9/490 |
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