Functional flexibility of a type III polyketide synthase in Mycobacterium marinum
Summary: Type III polyketide synthases (T3PKSs) exhibit remarkable potential to biosynthesize a wide array of architecturally distinct and functionally important metabolites. Genes for T3PKSs widely occur in pathogenic mycobacterial genomes, with no information about their physiological significance...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225013902 |
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| author | Umesh Prasad Sah Hathi Samir Giri Sonali Srivastava Gorkha Raj Giri Eira Choudhary Nisheeth Agarwal Priti Saxena |
| author_facet | Umesh Prasad Sah Hathi Samir Giri Sonali Srivastava Gorkha Raj Giri Eira Choudhary Nisheeth Agarwal Priti Saxena |
| author_sort | Umesh Prasad Sah Hathi |
| collection | DOAJ |
| description | Summary: Type III polyketide synthases (T3PKSs) exhibit remarkable potential to biosynthesize a wide array of architecturally distinct and functionally important metabolites. Genes for T3PKSs widely occur in pathogenic mycobacterial genomes, with no information about their physiological significance in pathogenesis. Here, we describe the biological importance of MMAR_2190, a M. marinum (Mmar) T3PKS, with orthologs in limited pathogenic mycobacterial species. High-resolution mass spectrometry revealed distinctive cyclization flexibility of MMAR_2190 to concurrently biosynthesize alkyl-resorcinols, acyl-phloroglucinols, and alkyl-α-pyrones from a single catalytic core. Investigation of Mmar biofilms revealed significant upregulation of the mmar_2190 gene and confirmed the expression of MMAR_2190 metabolites. A mmar_2190 deficient Mmar strain showed significant defect in biofilm formation, suggesting possible roles in pathogenesis. Our studies thus unfold unique functional flexibility demonstrated by the MMAR_2190 protein to generate molecular variability. |
| format | Article |
| id | doaj-art-f23c8d97aa5c45e68de1fb33a8e917bb |
| institution | Matheson Library |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-f23c8d97aa5c45e68de1fb33a8e917bb2025-07-31T04:53:42ZengElsevieriScience2589-00422025-08-01288113129Functional flexibility of a type III polyketide synthase in Mycobacterium marinumUmesh Prasad Sah Hathi0Samir Giri1Sonali Srivastava2Gorkha Raj Giri3Eira Choudhary4Nisheeth Agarwal5Priti Saxena6Chemical Biology Group, Faculty of Life Sciences and Biotechnology, South Asian University, Maidan Garhi, New Delhi 110068, IndiaChemical Biology Group, Faculty of Life Sciences and Biotechnology, South Asian University, Maidan Garhi, New Delhi 110068, IndiaNational Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, IndiaChemical Biology Group, Faculty of Life Sciences and Biotechnology, South Asian University, Maidan Garhi, New Delhi 110068, IndiaTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana (NCR Delhi) 121 001, IndiaTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana (NCR Delhi) 121 001, IndiaChemical Biology Group, Faculty of Life Sciences and Biotechnology, South Asian University, Maidan Garhi, New Delhi 110068, India; Corresponding authorSummary: Type III polyketide synthases (T3PKSs) exhibit remarkable potential to biosynthesize a wide array of architecturally distinct and functionally important metabolites. Genes for T3PKSs widely occur in pathogenic mycobacterial genomes, with no information about their physiological significance in pathogenesis. Here, we describe the biological importance of MMAR_2190, a M. marinum (Mmar) T3PKS, with orthologs in limited pathogenic mycobacterial species. High-resolution mass spectrometry revealed distinctive cyclization flexibility of MMAR_2190 to concurrently biosynthesize alkyl-resorcinols, acyl-phloroglucinols, and alkyl-α-pyrones from a single catalytic core. Investigation of Mmar biofilms revealed significant upregulation of the mmar_2190 gene and confirmed the expression of MMAR_2190 metabolites. A mmar_2190 deficient Mmar strain showed significant defect in biofilm formation, suggesting possible roles in pathogenesis. Our studies thus unfold unique functional flexibility demonstrated by the MMAR_2190 protein to generate molecular variability.http://www.sciencedirect.com/science/article/pii/S2589004225013902BiochemistryMicrobial physiologyMicrobiology |
| spellingShingle | Umesh Prasad Sah Hathi Samir Giri Sonali Srivastava Gorkha Raj Giri Eira Choudhary Nisheeth Agarwal Priti Saxena Functional flexibility of a type III polyketide synthase in Mycobacterium marinum iScience Biochemistry Microbial physiology Microbiology |
| title | Functional flexibility of a type III polyketide synthase in Mycobacterium marinum |
| title_full | Functional flexibility of a type III polyketide synthase in Mycobacterium marinum |
| title_fullStr | Functional flexibility of a type III polyketide synthase in Mycobacterium marinum |
| title_full_unstemmed | Functional flexibility of a type III polyketide synthase in Mycobacterium marinum |
| title_short | Functional flexibility of a type III polyketide synthase in Mycobacterium marinum |
| title_sort | functional flexibility of a type iii polyketide synthase in mycobacterium marinum |
| topic | Biochemistry Microbial physiology Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225013902 |
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