AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus
Abstract Background AdpA is a global regulator of morphological differentiation and secondary metabolism in Streptomyces, but the regulatory roles of the Streptomyces AdpA family on the biosynthesis of the natural product ε-poly-l-lysine (ε-PL) remain unidentified, and few studies have focused on in...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-022-01785-6 |
| _version_ | 1819210488901271552 |
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| author | Rui Huang Honglu Liu Wanwan Zhao Siqi Wang Shufang Wang Jun Cai Chao Yang |
| author_facet | Rui Huang Honglu Liu Wanwan Zhao Siqi Wang Shufang Wang Jun Cai Chao Yang |
| author_sort | Rui Huang |
| collection | DOAJ |
| description | Abstract Background AdpA is a global regulator of morphological differentiation and secondary metabolism in Streptomyces, but the regulatory roles of the Streptomyces AdpA family on the biosynthesis of the natural product ε-poly-l-lysine (ε-PL) remain unidentified, and few studies have focused on increasing the production of ε-PL by manipulating transcription factors in Streptomyces. Results In this study, we revealed the regulatory roles of different AdpA homologs in ε-PL biosynthesis and morphological differentiation and effectively promoted ε-PL production and sporulation in Streptomyces albulus NK660 by heterologously expressing adpA from S. neyagawaensis NRRLB-3092 (adpA Sn ). First, we identified a novel AdpA homolog named AdpA Sa in S. albulus NK660 and characterized its function as an activator of ε-PL biosynthesis and morphological differentiation. Subsequently, four heterologous AdpA homologs were selected to investigate their phylogenetic relationships and regulatory roles in S. albulus, and AdpA Sn was demonstrated to have the strongest ability to promote both ε-PL production and sporulation among these five AdpA proteins. The ε-PL yield of S. albulus heterologously expressing adpA Sn was approximately 3.6-fold higher than that of the control strain. Finally, we clarified the mechanism of AdpA Sn in enhancing ε-PL biosynthesis and its effect on ε-PL polymerization degree using real-time quantitative PCR, microscale thermophoresis and MALDI-TOF–MS. AdpA Sn was purified, and its seven direct targets, zwf, tal, pyk2, pta, ack, pepc and a transketolase gene (DC74_2409), were identified, suggesting that AdpA Sn may cause the redistribution of metabolic flux in central metabolism pathways, which subsequently provides more carbon skeletons and ATP for ε-PL biosynthesis in S. albulus. Conclusions Here, we characterized the positive regulatory roles of Streptomyces AdpA homologs in ε-PL biosynthesis and their effects on morphological differentiation and reported for the first time that AdpA Sn promotes ε-PL biosynthesis by affecting the transcription of its target genes in central metabolism pathways. These findings supply valuable insights into the regulatory roles of the Streptomyces AdpA family on ε-PL biosynthesis and morphological differentiation and suggest that AdpA Sn may be an effective global regulator for enhanced production of ε-PL and other valuable secondary metabolites in Streptomyces. |
| first_indexed | 2024-12-23T06:11:59Z |
| format | Article |
| id | doaj.art-ee6367ba2efd4f10b1136e3bb34127c0 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-12-23T06:11:59Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-ee6367ba2efd4f10b1136e3bb34127c02022-12-21T17:57:25ZengBMCMicrobial Cell Factories1475-28592022-04-0121112010.1186/s12934-022-01785-6AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulusRui Huang0Honglu Liu1Wanwan Zhao2Siqi Wang3Shufang Wang4Jun Cai5Chao Yang6Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityAbstract Background AdpA is a global regulator of morphological differentiation and secondary metabolism in Streptomyces, but the regulatory roles of the Streptomyces AdpA family on the biosynthesis of the natural product ε-poly-l-lysine (ε-PL) remain unidentified, and few studies have focused on increasing the production of ε-PL by manipulating transcription factors in Streptomyces. Results In this study, we revealed the regulatory roles of different AdpA homologs in ε-PL biosynthesis and morphological differentiation and effectively promoted ε-PL production and sporulation in Streptomyces albulus NK660 by heterologously expressing adpA from S. neyagawaensis NRRLB-3092 (adpA Sn ). First, we identified a novel AdpA homolog named AdpA Sa in S. albulus NK660 and characterized its function as an activator of ε-PL biosynthesis and morphological differentiation. Subsequently, four heterologous AdpA homologs were selected to investigate their phylogenetic relationships and regulatory roles in S. albulus, and AdpA Sn was demonstrated to have the strongest ability to promote both ε-PL production and sporulation among these five AdpA proteins. The ε-PL yield of S. albulus heterologously expressing adpA Sn was approximately 3.6-fold higher than that of the control strain. Finally, we clarified the mechanism of AdpA Sn in enhancing ε-PL biosynthesis and its effect on ε-PL polymerization degree using real-time quantitative PCR, microscale thermophoresis and MALDI-TOF–MS. AdpA Sn was purified, and its seven direct targets, zwf, tal, pyk2, pta, ack, pepc and a transketolase gene (DC74_2409), were identified, suggesting that AdpA Sn may cause the redistribution of metabolic flux in central metabolism pathways, which subsequently provides more carbon skeletons and ATP for ε-PL biosynthesis in S. albulus. Conclusions Here, we characterized the positive regulatory roles of Streptomyces AdpA homologs in ε-PL biosynthesis and their effects on morphological differentiation and reported for the first time that AdpA Sn promotes ε-PL biosynthesis by affecting the transcription of its target genes in central metabolism pathways. These findings supply valuable insights into the regulatory roles of the Streptomyces AdpA family on ε-PL biosynthesis and morphological differentiation and suggest that AdpA Sn may be an effective global regulator for enhanced production of ε-PL and other valuable secondary metabolites in Streptomyces.https://doi.org/10.1186/s12934-022-01785-6AdpAStreptomyces albulusε-Poly-l-lysinePolymerization degreeMorphological differentiation |
| spellingShingle | Rui Huang Honglu Liu Wanwan Zhao Siqi Wang Shufang Wang Jun Cai Chao Yang AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus Microbial Cell Factories AdpA Streptomyces albulus ε-Poly-l-lysine Polymerization degree Morphological differentiation |
| title | AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus |
| title_full | AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus |
| title_fullStr | AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus |
| title_full_unstemmed | AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus |
| title_short | AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus |
| title_sort | adpa a developmental regulator promotes ε poly l lysine biosynthesis in streptomyces albulus |
| topic | AdpA Streptomyces albulus ε-Poly-l-lysine Polymerization degree Morphological differentiation |
| url | https://doi.org/10.1186/s12934-022-01785-6 |
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