C-nucleoside antibiotics. 2. Synthesis of oxazinomycin (minimycin)

Bernardo, Silvano De; Weigele, Manfred

doi:10.1021/jo00421a021

Cited by 52 publications

(9 citation statements)

References 8 publications

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“…showed that the C-2 of MIN is derived from carbon dioxide (Isono and Suhadolnik, 1975). Concomitant chemical synthesis of MIN was also achieved, with the finding that the synthetic form of MIN shares identical biological features with that from microbial source (De Bernardo and Weigele, 1977).…”

Section: Introductionmentioning

confidence: 99%

Divergent Biosynthesis of C-Nucleoside Minimycin and Indigoidine in Bacteria

Kong

Liu

et al. 2019

iScience

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SummaryMinimycin (MIN) is a C-nucleoside antibiotic structurally related to pseudouridine, and indigoidine is a naturally occurring blue pigment produced by diverse bacteria. Although MIN and indigoidine have been known for decades, the logic underlying the divergent biosynthesis of these interesting molecules has been obscure. Here, we report the identification of a minimal 5-gene cluster (min) essential for MIN biosynthesis. We demonstrated that a non-ribosomal peptide synthetase (MinA) governs “the switch” for the divergent biosynthesis of MIN and the cryptic indigoidine. We also demonstrated that MinCN (the N-terminal phosphatase domain of MinC), MinD (uracil phosphoribosyltransferase), and MinT (transporter) function together as the safeguard enzymes, which collaboratively constitute an unusual self-resistance system. Finally, we provided evidence that MinD, utilizing an unprecedented substrate-competition strategy for self-resistance of the producer cell, maintains competition advantage over the active molecule MIN-5′-monophosphate by increasing the UMP pool in vivo. These findings greatly expand our knowledge regarding natural product biosynthesis.

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Section: Introductionmentioning

confidence: 99%

Divergent Biosynthesis of C-Nucleoside Minimycin and Indigoidine in Bacteria

Kong

Liu

et al. 2019

iScience

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“…and Pseudomonas sp. [ 21 – 23 ]. The MIN molecule distinguishes a unique structural system, in which the 1,3-oxazine-2,4-dione ring and the ribosyl sugar are linked via a C–C bond [ 24 ].…”

Section: Biosynthesis Of the Yein-like Type C -Nucleoside Antibioticsmentioning

confidence: 99%

Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments

et al. 2022

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Epidemic diseases and antibiotic resistance are urgent threats to global health, and human is confronted with an unprecedented dilemma to conquer them by expediting development of new natural product related drugs. C-nucleoside antibiotics, a remarkable group of microbial natural products with diverse biological activities, feature a heterocycle base linked with a ribosyl moiety via an unusual C-glycosidic bond, and have played significant roles in healthcare and for plant protection. Elucidating how nature biosynthesizes such a group of antibiotics has provided the basis for engineered biosynthesis as well as targeted genome mining of more C-nucleoside antibiotics towards improved properties. In this review, we mainly summarize the recent advances on the biosynthesis of C-nucleoside antibiotics, and we also tentatively discuss the future developments on rationally accessing C-nucleoside diversities in a more efficient and economical way via synthetic biology strategies.

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“…Tymiak et al. also reported its production from Pseudomonas paucimobilis (18), and the full chemical synthesis of OZM has been described (19). OZM is active against both gram positive and gram negative bacteria, and has antitumor activity against transplantable tumors (15,16).…”

Section: Introductionmentioning

confidence: 99%

Oxazinomycin arrests RNA polymerase at the polythymidine sequences

Prajapati

Rosenqvist

Palmu

et al. 2019

Nucleic Acids Research

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Oxazinomycin is a C-nucleoside antibiotic that is produced by Streptomyces hygroscopicus and closely resembles uridine. Here, we show that the oxazinomycin triphosphate is a good substrate for bacterial and eukaryotic RNA polymerases (RNAPs) and that a single incorporated oxazinomycin is rapidly extended by the next nucleotide. However, the incorporation of several successive oxazinomycins or a single oxazinomycin in a certain sequence context arrested a fraction of the transcribing RNAP. The addition of Gre RNA cleavage factors eliminated the transcriptional arrest at a single oxazinomycin and shortened the nascent RNAs arrested at the polythymidine sequences suggesting that the transcriptional arrest was caused by backtracking of RNAP along the DNA template. We further demonstrate that the ubiquitous C-nucleoside pseudouridine is also a good substrate for RNA polymerases in a triphosphorylated form but does not inhibit transcription of the polythymidine sequences. Our results collectively suggest that oxazinomycin functions as a Trojan horse substrate and its inhibitory effect is attributable to the oxygen atom in the position corresponding to carbon five of the uracil ring.

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C-nucleoside antibiotics. 2. Synthesis of oxazinomycin (minimycin)

Cited by 52 publications

References 8 publications

Divergent Biosynthesis of C-Nucleoside Minimycin and Indigoidine in Bacteria

Divergent Biosynthesis of C-Nucleoside Minimycin and Indigoidine in Bacteria

Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments

Oxazinomycin arrests RNA polymerase at the polythymidine sequences

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