Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic Pathway
Empedopeptins—eight amino acid cyclic lipopeptides—are calcium-dependent antibiotics that act against Gram-positive bacteria such as <i>Staphylococcus aureus</i> by inhibiting cell wall biosynthesis. However, to date, the biosynthetic mechanism of the empedopeptins has not been well iden...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/4/209 |
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| author | Shang-Tse Ho Ying-Ning Ho Chih Lin Wei-Chen Hsu Han-Jung Lee Chia-Chi Peng Han-Tan Cheng Yu-Liang Yang |
| author_facet | Shang-Tse Ho Ying-Ning Ho Chih Lin Wei-Chen Hsu Han-Jung Lee Chia-Chi Peng Han-Tan Cheng Yu-Liang Yang |
| author_sort | Shang-Tse Ho |
| collection | DOAJ |
| description | Empedopeptins—eight amino acid cyclic lipopeptides—are calcium-dependent antibiotics that act against Gram-positive bacteria such as <i>Staphylococcus aureus</i> by inhibiting cell wall biosynthesis. However, to date, the biosynthetic mechanism of the empedopeptins has not been well identified. Through comparative genomics and metabolomics analysis, we identified empedopeptin and its new analogs from a marine bacterium, <i>Massilia</i> sp. YMA4. We then unveiled the empedopeptin biosynthetic gene cluster. The core nonribosomal peptide gene null-mutant strains (Δ<i>empC</i>, Δ<i>empD</i>, and Δ<i>empE</i>) could not produce empedopeptin, while dioxygenase gene null-mutant strains (Δ<i>empA</i> and Δ<i>empB</i>) produced several unique empedopeptin analogs. However, the antibiotic activity of Δ<i>empA</i> and Δ<i>empB</i> was significantly reduced compared with the wild-type, demonstrating that the hydroxylated amino acid residues of empedopeptin and its analogs are important to their antibiotic activity. Furthermore, we found seven bacterial strains that could produce empedopeptin-like cyclic lipopeptides using a genome mining approach. In summary, this study demonstrated that an integrated omics strategy can facilitate the discovery of potential bioactive metabolites from microbial sources without further isolation and purification. |
| first_indexed | 2024-03-10T12:27:34Z |
| format | Article |
| id | doaj.art-f3ff78322a134c92bdee15e2ee7173d5 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T12:27:34Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-f3ff78322a134c92bdee15e2ee7173d52023-11-21T14:55:55ZengMDPI AGMarine Drugs1660-33972021-04-0119420910.3390/md19040209Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic PathwayShang-Tse Ho0Ying-Ning Ho1Chih Lin2Wei-Chen Hsu3Han-Jung Lee4Chia-Chi Peng5Han-Tan Cheng6Yu-Liang Yang7Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanInstitute of Marine Biology, College of Life Science, National Taiwan Ocean University, Keelung 20224, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, TaiwanEmpedopeptins—eight amino acid cyclic lipopeptides—are calcium-dependent antibiotics that act against Gram-positive bacteria such as <i>Staphylococcus aureus</i> by inhibiting cell wall biosynthesis. However, to date, the biosynthetic mechanism of the empedopeptins has not been well identified. Through comparative genomics and metabolomics analysis, we identified empedopeptin and its new analogs from a marine bacterium, <i>Massilia</i> sp. YMA4. We then unveiled the empedopeptin biosynthetic gene cluster. The core nonribosomal peptide gene null-mutant strains (Δ<i>empC</i>, Δ<i>empD</i>, and Δ<i>empE</i>) could not produce empedopeptin, while dioxygenase gene null-mutant strains (Δ<i>empA</i> and Δ<i>empB</i>) produced several unique empedopeptin analogs. However, the antibiotic activity of Δ<i>empA</i> and Δ<i>empB</i> was significantly reduced compared with the wild-type, demonstrating that the hydroxylated amino acid residues of empedopeptin and its analogs are important to their antibiotic activity. Furthermore, we found seven bacterial strains that could produce empedopeptin-like cyclic lipopeptides using a genome mining approach. In summary, this study demonstrated that an integrated omics strategy can facilitate the discovery of potential bioactive metabolites from microbial sources without further isolation and purification.https://www.mdpi.com/1660-3397/19/4/209<i>Massilia</i>lipopeptidesbiosynthesisgenome miningmetabolomics |
| spellingShingle | Shang-Tse Ho Ying-Ning Ho Chih Lin Wei-Chen Hsu Han-Jung Lee Chia-Chi Peng Han-Tan Cheng Yu-Liang Yang Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic Pathway Marine Drugs <i>Massilia</i> lipopeptides biosynthesis genome mining metabolomics |
| title | Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic Pathway |
| title_full | Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic Pathway |
| title_fullStr | Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic Pathway |
| title_full_unstemmed | Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic Pathway |
| title_short | Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from <em>Massilia</em> sp. YMA4 and Their Biosynthetic Pathway |
| title_sort | integrated omics strategy reveals cyclic lipopeptides empedopeptins from em massilia em sp yma4 and their biosynthetic pathway |
| topic | <i>Massilia</i> lipopeptides biosynthesis genome mining metabolomics |
| url | https://www.mdpi.com/1660-3397/19/4/209 |
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