Abyssomicin Biosynthesis: Formation of an Unusual Polyketide, Antibiotic‐Feeding Studies and Genetic Analysis

Gottardi, Elvira; Krawczyk, Joanna M.; Suchodoletz, Hanna von; Schadt, Heiko S.; Mühlenweg, Agnes; Uguru, Gabriel C.; Pelzer, Stefan; Fiedler, Hans‐Peter; Bibb, Mervyn J.; Stach, James E. M.; Süssmuth, Roderich D.

doi:10.1002/cbic.201100172

Cited by 68 publications

(61 citation statements)

References 64 publications

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“…Comparison with other biosynthetic studies of tetronate antibiotics aided in the identification of genes responsible for abyssomicin C biosynthesis; three genes encoding for proteins for the generation of the polyketide backbone (which effectively forms the macrocycle in abyssomicin C); five genes encoding for proteins involved in the generation of the tetronate moiety; three genes for further oxidative enzymes; and a variety of other genes related to import, export and packaging of the molecule. 57 It was noted that the structure of 23 and 24 were similar to that of chorismate, a precursor to PABA, 58 and studies revealed that atrop-abyssomicin irreversibly binds the Cys263 of E. coli 4-amino-4-deoxychorismate in a Michael addition, forming a sulphur-bound abyssomicin D in the process. 47 This mechanism is attributed to the α,β-unsaturated ketone, which is not present in other detected abyssomicins.…”

Section: Abyssomicin C: a Promising Antibacterial For Tuberculosismentioning

confidence: 94%

A twist of nature – the significance of atropisomers in biological systems

2015

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. (2015). A twist of nature-the significance of atropisomers in biological systems. Natural Product Reports: a journal of current development in bioorganic chemistry, 32 (11), 1562-1583. A twist of nature-the significance of atropisomers in biological systems AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized. AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized.

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Section: Abyssomicin C: a Promising Antibacterial For Tuberculosismentioning

confidence: 94%

A twist of nature – the significance of atropisomers in biological systems

2015

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“…Based on a similar reaction which has been suggested for abyssomicin (Fig. 1B), 71 we propose that the cyclization resulting in this heterocyclic ring would proceed through two steps. First, the alkene present at C-14/C-15 in intermediate 12 would undergo an epoxidation giving intermediate 13.…”

Section: Biosynthesismentioning

confidence: 84%

Tetrodecamycin: An unusual and interesting tetronate antibiotic

Gverzdys

Kramer

Nodwell

2016

Bioorganic & Medicinal Chemistry

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The tetrodecamycins are a group of secondary metabolites that are characterized by the presence of a tetronate ring in their structure. Originally discovered for their antibiotic activity against Photobacterium damselae ssp. piscicida, the causative agent of pseudotuberculosis in fish, this family of molecules has also been shown to have potent antibiotic activity against methicillin-resistant Staphylococcus aureus. Due to their small size and highly cyclized nature, they represent an unusual member of the much larger group of bioactive molecules called the tetronates. Herein, we review what is known about the mechanism of action of these molecules and also present a hypothesis for their biosynthesis. A deeper understanding of the tetrodecamycins will provide a more holistic view of the tetronate-family, provide new chemical probes of bacterial biology, and may provide therapeutic lead molecules.

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“…PKS domains are shown as circles. Adapted from Gottardi et al (2011). which follow have the same basic set, each extended by DH and KR domains arranged in the biosynthetic assembly line. Module 5 of abyB2 has the same arrangement of module 4, but the DH and KR domains are likely to be inactive.…”

Section: Secondary Metabolites Synthesised By Pks Gene Clustermentioning

confidence: 99%

“…There are also genes encoding oxygenases, as well as genes with putative regulatory and export functions involved in the abyssomicin biosynthesis. Formation of abyssomicin C requires two propionates, five acetates and one glucose-derived metabolite (Gottardi et al, 2011).…”

Section: Secondary Metabolites Synthesised By Pks Gene Clustermentioning

confidence: 99%