Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host
Ilamycins are cyclopeptides with novel structures that have been isolated from different <i>Actinomycetes</i>. They showed strong anti-tuberculosis activity and could serve as important anti-tuberculosis drug leads. The functions of the pre-tailoring and the post-tailoring genes in the b...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/4/216 |
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| author | Jianqiao He Xin Wei Zhijie Yang Yan Li Jianhua Ju Junying Ma |
| author_facet | Jianqiao He Xin Wei Zhijie Yang Yan Li Jianhua Ju Junying Ma |
| author_sort | Jianqiao He |
| collection | DOAJ |
| description | Ilamycins are cyclopeptides with novel structures that have been isolated from different <i>Actinomycetes</i>. They showed strong anti-tuberculosis activity and could serve as important anti-tuberculosis drug leads. The functions of the pre-tailoring and the post-tailoring genes in the biosynthesis of ilamycins have been elucidated, but the functions of the regulatory and transporter genes remain elusive. We reported herein the functions of four genes in ilamycin biosynthetic gene cluster (<i>ila</i> BGC) including two regulatory genes (<i>ilaA</i> and <i>ilaB</i>) and two transporter genes (<i>ilaJ</i> and <i>ilaK</i>) and the heterologous expression of <i>ila</i> BGC. The IlaA and IlaB were unambiguously shown to be negative and positive regulator of ilamycins biosynthesis, respectively. Consistent with these roles, inactivation of <i>ilaA</i> and <i>ilaB</i> (independent of each other) was shown to enhance and abolish the production of ilamycins, respectively. Total yields of ilamycins were enhanced 3.0-fold and 1.9-fold by inactivation of <i>ilaA</i> and overexpression of <i>ilaB</i> compared to those of in the <i>Streptomyces atratus</i> SCSIO ZH16, respectively. In addition, the <i>ila</i> BGC was successfully expressed in <i>Streptomyces coelicolor</i> M1152, which indicated that all biosynthetic elements for the construction of ilamycins were included in the PAC7A6. These results not only lay a foundation for further exploration of ilamycins, but also provide the genetic elements for synthetic biology. |
| first_indexed | 2024-03-10T20:24:10Z |
| format | Article |
| id | doaj.art-5e34a758d86d47a08584349d84705a73 |
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| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T20:24:10Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
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| series | Marine Drugs |
| spelling | doaj.art-5e34a758d86d47a08584349d84705a732023-11-19T21:54:38ZengMDPI AGMarine Drugs1660-33972020-04-0118421610.3390/md18040216Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous HostJianqiao He0Xin Wei1Zhijie Yang2Yan Li3Jianhua Ju4Junying Ma5CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaIlamycins are cyclopeptides with novel structures that have been isolated from different <i>Actinomycetes</i>. They showed strong anti-tuberculosis activity and could serve as important anti-tuberculosis drug leads. The functions of the pre-tailoring and the post-tailoring genes in the biosynthesis of ilamycins have been elucidated, but the functions of the regulatory and transporter genes remain elusive. We reported herein the functions of four genes in ilamycin biosynthetic gene cluster (<i>ila</i> BGC) including two regulatory genes (<i>ilaA</i> and <i>ilaB</i>) and two transporter genes (<i>ilaJ</i> and <i>ilaK</i>) and the heterologous expression of <i>ila</i> BGC. The IlaA and IlaB were unambiguously shown to be negative and positive regulator of ilamycins biosynthesis, respectively. Consistent with these roles, inactivation of <i>ilaA</i> and <i>ilaB</i> (independent of each other) was shown to enhance and abolish the production of ilamycins, respectively. Total yields of ilamycins were enhanced 3.0-fold and 1.9-fold by inactivation of <i>ilaA</i> and overexpression of <i>ilaB</i> compared to those of in the <i>Streptomyces atratus</i> SCSIO ZH16, respectively. In addition, the <i>ila</i> BGC was successfully expressed in <i>Streptomyces coelicolor</i> M1152, which indicated that all biosynthetic elements for the construction of ilamycins were included in the PAC7A6. These results not only lay a foundation for further exploration of ilamycins, but also provide the genetic elements for synthetic biology.https://www.mdpi.com/1660-3397/18/4/216marine-derived <i>Streptomyces</i>ilamycinsregulatorABC-transporterheterologous expression |
| spellingShingle | Jianqiao He Xin Wei Zhijie Yang Yan Li Jianhua Ju Junying Ma Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host Marine Drugs marine-derived <i>Streptomyces</i> ilamycins regulator ABC-transporter heterologous expression |
| title | Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host |
| title_full | Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host |
| title_fullStr | Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host |
| title_full_unstemmed | Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host |
| title_short | Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host |
| title_sort | characterization of regulatory and transporter genes in the biosynthesis of anti tuberculosis ilamycins and production in a heterologous host |
| topic | marine-derived <i>Streptomyces</i> ilamycins regulator ABC-transporter heterologous expression |
| url | https://www.mdpi.com/1660-3397/18/4/216 |
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