Biosynthetic rivalry of o-aminophenol-carboxylic acids initiates production of hemi-actinomycins in Streptomyces antibioticus
| dc.contributor.author | Crnovčić, Ivana | |
| dc.contributor.author | Semsary, Siamak | |
| dc.contributor.author | Vater, Joachim | |
| dc.contributor.author | Keller, Ullrich | |
| dc.date.accessioned | 2016-06-23T06:47:25Z | |
| dc.date.available | 2016-06-23T06:47:25Z | |
| dc.date.issued | 2014 | |
| dc.description | Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich. | de |
| dc.description | This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. | en |
| dc.description.abstract | Actinomycins consist of two pentapeptide lactone rings attached to 2-amino-4,6-dimethyl-3-oxo-phenoxazine-1,9-dicarboxylic acid (actinocin). The actinocin moiety is formed through oxidative condensation of two 3-hydroxy-4-methylanthranilic acid (4-MHA) pentapeptide lactones (actinomycin halves) as the last step of actinomycin biosynthesis. We found that feeding of 4-MHA or its putative biogenetic precursor 3-hydroxyanthranilic acid (3-HA) to Streptomyces antibioticus induced formation of different new compounds at the expense of actinomycins. These contain only one pentapeptide lactone ring attached to the β-side of their phenoxazinone ring systems and are formed through premature condensation of the externally added abundant 4-MHA or 3-HA with actinomycin halves. They were termed hemi-actinomycins and C-demethyl-hemi-actinomycins, respectively, which differ from each other in the presence or absence of one or both methyl groups in their phenoxazinone moieties. 3-HA also induces synthesis of various C-demethylactinomycins formed through condensation of actinomycin halves in which 3-HA had been incorporated by the 4-MHA incorporating enzyme in lieu of 4-MHA. 3-HA was not converted to 4-MHA as revealed by its inability to stimulate synthesis of actinomycin or hemi-actinomycin synthesis and thus remained a substrate analogue of 4-MHA rather than its precursor. In contrast to S. antibioticus, actinomycin-producing streptomycetes such as Streptomyces chrysomallus or Streptomyces parvulus do not form hemi-structured actinomycins when fed with 3-HA or 4-MHA. They do not possess the enzyme phenoxazinone synthase (PHS) which in S. antibioticus is present and most probably catalyses premature condensation of abundant 4-MHA or 3-HA with actinomycin halves. Testing hemi-acinomycin IV for drug activity revealed that it intercalates into DNA and inhibits relaxation and supertwisting of DNA by topoisomerase I and DNA-gyrase like actinomycin IV (D). Moreover, it has inhibitory activity on growth of Bacillus subtilis. | en |
| dc.description.sponsorship | DFG, EXC 314, Unifying Concepts in Catalysis | en |
| dc.identifier.eissn | 2046-2069 | |
| dc.identifier.uri | https://depositonce.tu-berlin.de/handle/11303/5619 | |
| dc.identifier.uri | http://dx.doi.org/10.14279/depositonce-5248 | |
| dc.language.iso | en | |
| dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | en |
| dc.subject.ddc | 540 Chemie und zugeordnete Wissenschaften | de |
| dc.title | Biosynthetic rivalry of o-aminophenol-carboxylic acids initiates production of hemi-actinomycins in Streptomyces antibioticus | en |
| dc.type | Article | en |
| dc.type.version | publishedVersion | en |
| dcterms.bibliographicCitation.doi | 10.1039/c3ra45661g | |
| dcterms.bibliographicCitation.issue | 10 | |
| dcterms.bibliographicCitation.journaltitle | RSC Advances : an international journal to further the chemical sciences | en |
| dcterms.bibliographicCitation.originalpublishername | Royal Society of Chemistry | de |
| dcterms.bibliographicCitation.originalpublisherplace | Cambridge | de |
| dcterms.bibliographicCitation.pageend | 5074 | |
| dcterms.bibliographicCitation.pagestart | 5065 | |
| dcterms.bibliographicCitation.volume | 4 | |
| tub.accessrights.dnb | domain | |
| tub.affiliation | Fak. 2 Mathematik und Naturwissenschaften::Inst. Chemie | de |
| tub.affiliation.faculty | Fak. 2 Mathematik und Naturwissenschaften | de |
| tub.affiliation.institute | Inst. Chemie | de |
| tub.publisher.universityorinstitution | Technische Universität Berlin |
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