Mechanism and regulation of sorbicillin biosynthesis by Penicillium chrysogenum
| العنوان: | Mechanism and regulation of sorbicillin biosynthesis by Penicillium chrysogenum |
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| المؤلفون: | Fernando Guzmán-Chávez, Yvonne Nygård, Oleksandr Salo, Arnold J. M. Driessen, Peter P. Lankhorst, Roel A. L. Bovenberg |
| المساهمون: | Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology |
| المصدر: | Microbial Biotechnology, 10(4), 958-968. Wiley Microbial Biotechnology |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, EXPRESSION, STRAIN, FUNGAL SECONDARY METABOLISM, Gene Expression, Bioengineering, Penicillium chrysogenum, Applied Microbiology and Biotechnology, Biochemistry, Fungal Proteins, PATHWAY, 03 medical and health sciences, Polyketide, chemistry.chemical_compound, Biosynthesis, Transcription (biology), Oxidoreductase, Gene Expression Regulation, Fungal, Polyketide synthase, Journal Article, Metabolomics, Gene, PRECURSOR, Research Articles, chemistry.chemical_classification, ANALOGS, biology, Resorcinols, Monooxygenase, FILAMENTOUS FUNGI, biology.organism_classification, Biosynthetic Pathways, GENE CLUSTERS, 030104 developmental biology, chemistry, BISORBICILLINOIDS, biology.protein, Gene Deletion, Research Article, Biotechnology, TRICHODERMA SP |
| الوصف: | Summary Penicillium chrysogenum is a filamentous fungus that is used to produce β‐lactams at an industrial scale. At an early stage of classical strain improvement, the ability to produce the yellow‐coloured sorbicillinoids was lost through mutation. Sorbicillinoids are highly bioactive of great pharmaceutical interest. By repair of a critical mutation in one of the two polyketide synthases in an industrial P. chrysogenum strain, sorbicillinoid production was restored at high levels. Using this strain, the sorbicillin biosynthesis pathway was elucidated through gene deletion, overexpression and metabolite profiling. The polyketide synthase enzymes SorA and SorB are required to generate the key intermediates sorbicillin and dihydrosorbicillin, which are subsequently converted to (dihydro)sorbillinol by the FAD‐dependent monooxygenase SorC and into the final product oxosorbicillinol by the oxidoreductase SorD. Deletion of either of the two pks genes not only impacted the overall production but also strongly reduce the expression of the pathway genes. Expression is regulated through the interplay of two transcriptional regulators: SorR1 and SorR2. SorR1 acts as a transcriptional activator, while SorR2 controls the expression of sorR1. Furthermore, the sorbicillinoid pathway is regulated through a novel autoinduction mechanism where sorbicillinoids activate transcription. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1751-7915 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b85a2cef15df9b7b2fa129926643003 https://research.rug.nl/en/publications/532adfd5-3399-4531-afee-5bcf43120054 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5b85a2cef15df9b7b2fa129926643003 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17517915 |
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