Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites
<i>Malbranchea circinata</i> SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/23/1/50 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588072805466112 |
|---|---|
| author | Hu Yang Xiaowei Luo Zhuo Shang Kunlong Li Jian Cai Yingying Chen Longchao Xin Jianhua Ju |
| author_facet | Hu Yang Xiaowei Luo Zhuo Shang Kunlong Li Jian Cai Yingying Chen Longchao Xin Jianhua Ju |
| author_sort | Hu Yang |
| collection | DOAJ |
| description | <i>Malbranchea circinata</i> SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type <i>M. circinata</i> SDU050, alongside five additional metabolite classes, including three novel cytochalasins (<b>7</b>–<b>9</b>), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (<b>1</b>) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (<b>1</b>) and (−)-mycousnine (<b>10</b>) exhibited weak antibacterial activity against Gram-positive bacteria such as <i>Staphylococcus aureus</i>, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), and <i>Bacillus subtilis</i>. These findings underscore the chemical diversity and biosynthetic potential of <i>M. circinata</i> SDU050 and highlight an effective strategy for exploring marine fungal metabolites. |
| format | Article |
| id | doaj-art-8ccddb1c099f4f7c9ede8873dc9e7214 |
| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-8ccddb1c099f4f7c9ede8873dc9e72142025-01-24T13:39:38ZengMDPI AGMarine Drugs1660-33972025-01-012315010.3390/md23010050Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary MetabolitesHu Yang0Xiaowei Luo1Zhuo Shang2Kunlong Li3Jian Cai4Yingying Chen5Longchao Xin6Jianhua Ju7Key Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaGuangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-Efficient Utilization of Marine Traditional Chinese Medicine Resources, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, ChinaKey Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaKey Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaKey Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaKey Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China<i>Malbranchea circinata</i> SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type <i>M. circinata</i> SDU050, alongside five additional metabolite classes, including three novel cytochalasins (<b>7</b>–<b>9</b>), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (<b>1</b>) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (<b>1</b>) and (−)-mycousnine (<b>10</b>) exhibited weak antibacterial activity against Gram-positive bacteria such as <i>Staphylococcus aureus</i>, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), and <i>Bacillus subtilis</i>. These findings underscore the chemical diversity and biosynthetic potential of <i>M. circinata</i> SDU050 and highlight an effective strategy for exploring marine fungal metabolites.https://www.mdpi.com/1660-3397/23/1/50secondary metabolitesfungideep-sea sedimentmetabolic blockadecytochalasin |
| spellingShingle | Hu Yang Xiaowei Luo Zhuo Shang Kunlong Li Jian Cai Yingying Chen Longchao Xin Jianhua Ju Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites Marine Drugs secondary metabolites fungi deep-sea sediment metabolic blockade cytochalasin |
| title | Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites |
| title_full | Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites |
| title_fullStr | Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites |
| title_full_unstemmed | Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites |
| title_short | Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites |
| title_sort | metabolic blockade based genome mining of i malbranchea circinata i sdu050 discovery of diverse secondary metabolites |
| topic | secondary metabolites fungi deep-sea sediment metabolic blockade cytochalasin |
| url | https://www.mdpi.com/1660-3397/23/1/50 |
| work_keys_str_mv | AT huyang metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites AT xiaoweiluo metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites AT zhuoshang metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites AT kunlongli metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites AT jiancai metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites AT yingyingchen metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites AT longchaoxin metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites AT jianhuaju metabolicblockadebasedgenomeminingofimalbrancheacircinataisdu050discoveryofdiversesecondarymetabolites |