The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes
Streptomycetes are important biotechnological bacteria that produce several clinically bioactive compounds. They have a complex development, including hyphae differentiation and sporulation. Cytosolic copper is a well-known modulator of differentiation and secondary metabolism. The interruption of t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/10143 |
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| author | Nathaly González-Quiñónez Ignacio Gutiérrez-Del-Río Paula García-Cancela Gemma Fernández-García Sergio Alonso-Fernández Paula Yagüe Álvaro Pérez-Valero María Montes-Bayón Felipe Lombó Ángel Manteca |
| author_facet | Nathaly González-Quiñónez Ignacio Gutiérrez-Del-Río Paula García-Cancela Gemma Fernández-García Sergio Alonso-Fernández Paula Yagüe Álvaro Pérez-Valero María Montes-Bayón Felipe Lombó Ángel Manteca |
| author_sort | Nathaly González-Quiñónez |
| collection | DOAJ |
| description | Streptomycetes are important biotechnological bacteria that produce several clinically bioactive compounds. They have a complex development, including hyphae differentiation and sporulation. Cytosolic copper is a well-known modulator of differentiation and secondary metabolism. The interruption of the <i>Streptomyces coelicolor SCO2730</i> (copper chaperone, <i>SCO2730::Tn5062</i> mutant) blocks <i>SCO2730</i> and reduces <i>SCO2731</i> (P-type ATPase copper export) expressions, decreasing copper export and increasing cytosolic copper. This mutation triggers the expression of 13 secondary metabolite clusters, including cryptic pathways, during the whole developmental cycle, skipping the vegetative, non-productive stage. As a proof of concept, here, we tested whether the knockdown of the <i>SCO2730/31</i> orthologue expression can enhance secondary metabolism in streptomycetes. We created a <i>SCO2730/31</i> consensus antisense mRNA from the sequences of seven key streptomycetes, which helped to increase the cytosolic copper in <i>S. coelicolor</i>, albeit to a lower level than in the <i>SCO2730::Tn5062</i> mutant. This antisense mRNA affected the production of at least six secondary metabolites (CDA, 2-methylisoborneol, undecylprodigiosin, tetrahydroxynaphtalene, α-actinorhodin, ε-actinorhodin) in the <i>S. coelicolor</i>, and five (phenanthroviridin, alkylresorcinol, chloramphenicol, pikromycin, jadomycin G) in the <i>S. venezuelae</i>; it also helped to alter the <i>S. albus</i> metabolome. The <i>SCO2730/31</i> consensus antisense mRNA designed here constitutes a tool for the knockdown of <i>SCO2730/31</i> expression and for the enhancement of <i>Streptomyces</i>’ secondary metabolism. |
| first_indexed | 2024-03-10T07:34:57Z |
| format | Article |
| id | doaj.art-885829c70d0f4713a767f1dc97324bb9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:34:57Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-885829c70d0f4713a767f1dc97324bb92023-11-22T13:33:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122181014310.3390/ijms221810143The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in StreptomycetesNathaly González-Quiñónez0Ignacio Gutiérrez-Del-Río1Paula García-Cancela2Gemma Fernández-García3Sergio Alonso-Fernández4Paula Yagüe5Álvaro Pérez-Valero6María Montes-Bayón7Felipe Lombó8Ángel Manteca9Área de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainÁrea de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainDepartment of Physical and Analytical Chemistry, ISPA, Faculty of Chemistry, Universidad de Oviedo, 33006 Oviedo, SpainÁrea de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainÁrea de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainÁrea de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainÁrea de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainDepartment of Physical and Analytical Chemistry, ISPA, Faculty of Chemistry, Universidad de Oviedo, 33006 Oviedo, SpainÁrea de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainÁrea de Microbiología, Departamento de Biología Funcional, IUOPA, ISPA, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, SpainStreptomycetes are important biotechnological bacteria that produce several clinically bioactive compounds. They have a complex development, including hyphae differentiation and sporulation. Cytosolic copper is a well-known modulator of differentiation and secondary metabolism. The interruption of the <i>Streptomyces coelicolor SCO2730</i> (copper chaperone, <i>SCO2730::Tn5062</i> mutant) blocks <i>SCO2730</i> and reduces <i>SCO2731</i> (P-type ATPase copper export) expressions, decreasing copper export and increasing cytosolic copper. This mutation triggers the expression of 13 secondary metabolite clusters, including cryptic pathways, during the whole developmental cycle, skipping the vegetative, non-productive stage. As a proof of concept, here, we tested whether the knockdown of the <i>SCO2730/31</i> orthologue expression can enhance secondary metabolism in streptomycetes. We created a <i>SCO2730/31</i> consensus antisense mRNA from the sequences of seven key streptomycetes, which helped to increase the cytosolic copper in <i>S. coelicolor</i>, albeit to a lower level than in the <i>SCO2730::Tn5062</i> mutant. This antisense mRNA affected the production of at least six secondary metabolites (CDA, 2-methylisoborneol, undecylprodigiosin, tetrahydroxynaphtalene, α-actinorhodin, ε-actinorhodin) in the <i>S. coelicolor</i>, and five (phenanthroviridin, alkylresorcinol, chloramphenicol, pikromycin, jadomycin G) in the <i>S. venezuelae</i>; it also helped to alter the <i>S. albus</i> metabolome. The <i>SCO2730/31</i> consensus antisense mRNA designed here constitutes a tool for the knockdown of <i>SCO2730/31</i> expression and for the enhancement of <i>Streptomyces</i>’ secondary metabolism.https://www.mdpi.com/1422-0067/22/18/10143<i>Streptomyces</i>differentiationcoppersecondary metabolism |
| spellingShingle | Nathaly González-Quiñónez Ignacio Gutiérrez-Del-Río Paula García-Cancela Gemma Fernández-García Sergio Alonso-Fernández Paula Yagüe Álvaro Pérez-Valero María Montes-Bayón Felipe Lombó Ángel Manteca The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes International Journal of Molecular Sciences <i>Streptomyces</i> differentiation copper secondary metabolism |
| title | The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes |
| title_full | The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes |
| title_fullStr | The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes |
| title_full_unstemmed | The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes |
| title_short | The Modulation of <i>SCO2730/31</i> Copper Chaperone/Transporter Orthologue Expression Enhances Secondary Metabolism in Streptomycetes |
| title_sort | modulation of i sco2730 31 i copper chaperone transporter orthologue expression enhances secondary metabolism in streptomycetes |
| topic | <i>Streptomyces</i> differentiation copper secondary metabolism |
| url | https://www.mdpi.com/1422-0067/22/18/10143 |
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