The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic
The type I polyketide SF2487/A80577 (herein referred to as tetromadurin) is a polyether tetronate ionophore antibiotic produced by the terrestrial Gram-positive bacterium Actinomadura verrucosospora. Tetromadurin is closely related to the polyether tetronates tetronasin (M139603) and tetronomycin, a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489565/?tool=EBI |
| _version_ | 1818532834549170176 |
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| author | Rory F. Little Markiyan Samborskyy Peter F. Leadlay Patrick C. Cirino |
| author_facet | Rory F. Little Markiyan Samborskyy Peter F. Leadlay Patrick C. Cirino |
| author_sort | Rory F. Little |
| collection | DOAJ |
| description | The type I polyketide SF2487/A80577 (herein referred to as tetromadurin) is a polyether tetronate ionophore antibiotic produced by the terrestrial Gram-positive bacterium Actinomadura verrucosospora. Tetromadurin is closely related to the polyether tetronates tetronasin (M139603) and tetronomycin, all of which are characterised by containing a tetronate, cyclohexane, tetrahydropyran, and at least one tetrahydrofuran ring. We have sequenced the genome of Actinomadura verrucosospora to identify the biosynthetic gene cluster responsible for tetromadurin biosynthesis (the mad gene cluster). Based on bioinformatic analysis of the 32 genes present within the cluster a plausible biosynthetic pathway for tetromadurin biosynthesis is proposed. Functional confirmation of the mad gene cluster is obtained by performing in-frame deletions in each of the genes mad10 and mad31, which encode putative cyclase enzymes responsible for cyclohexane and tetrahydropyran formation, respectively. Furthermore, the A. verrucosospora Δmad10 mutant produces a novel tetromadurin metabolite that according to mass spectrometry analysis is analogous to the recently characterised partially cyclised tetronasin intermediate lacking its cyclohexane and tetrahydropyran rings. Our results therefore elucidate the biosynthetic machinery of tetromadurin biosynthesis and lend support for a conserved mechanism of cyclohexane and tetrahydropyran biosynthesis across polyether tetronates. |
| first_indexed | 2024-12-11T17:50:42Z |
| format | Article |
| id | doaj.art-39e4d3e083864f168d6b77709c12503a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T17:50:42Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-39e4d3e083864f168d6b77709c12503a2022-12-22T00:56:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01159The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibioticRory F. LittleMarkiyan SamborskyyPeter F. LeadlayPatrick C. CirinoThe type I polyketide SF2487/A80577 (herein referred to as tetromadurin) is a polyether tetronate ionophore antibiotic produced by the terrestrial Gram-positive bacterium Actinomadura verrucosospora. Tetromadurin is closely related to the polyether tetronates tetronasin (M139603) and tetronomycin, all of which are characterised by containing a tetronate, cyclohexane, tetrahydropyran, and at least one tetrahydrofuran ring. We have sequenced the genome of Actinomadura verrucosospora to identify the biosynthetic gene cluster responsible for tetromadurin biosynthesis (the mad gene cluster). Based on bioinformatic analysis of the 32 genes present within the cluster a plausible biosynthetic pathway for tetromadurin biosynthesis is proposed. Functional confirmation of the mad gene cluster is obtained by performing in-frame deletions in each of the genes mad10 and mad31, which encode putative cyclase enzymes responsible for cyclohexane and tetrahydropyran formation, respectively. Furthermore, the A. verrucosospora Δmad10 mutant produces a novel tetromadurin metabolite that according to mass spectrometry analysis is analogous to the recently characterised partially cyclised tetronasin intermediate lacking its cyclohexane and tetrahydropyran rings. Our results therefore elucidate the biosynthetic machinery of tetromadurin biosynthesis and lend support for a conserved mechanism of cyclohexane and tetrahydropyran biosynthesis across polyether tetronates.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489565/?tool=EBI |
| spellingShingle | Rory F. Little Markiyan Samborskyy Peter F. Leadlay Patrick C. Cirino The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic PLoS ONE |
| title | The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic |
| title_full | The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic |
| title_fullStr | The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic |
| title_full_unstemmed | The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic |
| title_short | The biosynthetic pathway to tetromadurin (SF2487/A80577), a polyether tetronate antibiotic |
| title_sort | biosynthetic pathway to tetromadurin sf2487 a80577 a polyether tetronate antibiotic |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489565/?tool=EBI |
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