Summary The biosynthetic pathway of the red‐pigmented antibiotic, prodigiosin, produced by Serratia sp. is known to involve separate pathways for production monopyrrole, 2‐methyl‐3‐n‐amyl‐pyrrole (MAP) and bipyrrole, 4‐methoxy‐2,2′‐bipyrrole‐5‐carbaldehyde (MBC) which are then coupled in final condensation step. We have previously reported cloning, sequencing heterologous expression pig cluster responsible prodigiosin biosynthesis two In this article we report creation in‐frame deletions or...

The prodigiosin biosynthesis gene cluster ( pig cluster) from two strains of Serratia S. marcescens ATCC 274 and sp. 39006) has been cloned, sequenced expressed in heterologous hosts. Sequence analysis the respective clusters revealed 14 ORFs 15 39006. In each species, predicted products showed similarity to polyketide synthases (PKSs), non-ribosomal peptide (NRPSs) Red proteins Streptomyces coelicolor A3(2). Comparisons between red Str. A3(2) some important differences. A modified scheme...

Chiral bicyclic 1,2,4-triazolium salts having a defined face of the heterocyclic ring hindered have been synthesised and they catalyse benzoin condensation in good yield; enantiomeric excesses obtained (up to 80%) are much better than with closely related thiazolium opposite enantiomer predominates.

Bacterial prodiginines are a family of red-pigmented, tripyrrolic compounds that display numerous biological activities, including antibacterial, antifungal, antiprotozoal, antimalarial, immunosuppressive and anticancer properties. Recently, significant progress has been made in understanding the biosynthesis regulation bacterial prodiginines. An will allow engineering strains capable synthesizing novel through rational design mutasynthesis experiments. synthetic derivatives effective...

We show here that isonitriles can perform click reactions with tetrazines in aqueous media, making them promising candidates for ligation chemical biology and polymer chemistry. This is the first time a [4+1] cycloaddition has been used as biocompatible reaction.

Abstract Vitamin B 12 is an essential vitamin for human health, and lack of it leads to pernicious anemia. This biological activity has attracted intense interest some time; in addition, the complex architecture molecule fascinated chemists biochemists since its discovery as first natural organocobalt establishment structure by X‐ray analysis. The organic ligand surrounding cobalt displays many stereogenic centers along periphery carrying reactive functional groups. complexity led be rightly...

Seeing the sugar coating: N-Acetyl-glucosamine and mannosamine derivatives tagged with an isonitrile group are metabolically incorporated into cell-surface glycans can be detected a fluorescent tetrazine. This bioorthogonal isonitrile–tetrazine ligation is also orthogonal to commonly used azide-cyclooctyne ligation, so will allow simultaneous detection of incorporation two different sugars.

Cell surface glycans are involved in numerous physiological processes that involve cell-cell interactions and migration, including lymphocyte trafficking cancer metastasis. We have used a bioorthogonal metabolic labeling strategy to detect cell demonstrate, for the first time, fluorescence radionuclide imaging of sialylated murine tumor model vivo. Peracetylated azido-labeled N-acetyl-man-nosamine, injected intraperitoneally, was as precursor biosynthesis 5-azidoneuraminic, or azidosialic...

Abstract Bottromycin A 2 is a structurally unique ribosomally synthesized and post‐translationally modified peptide (RiPP) that possesses potent antibacterial activity towards multidrug‐resistant bacteria. The structural novelty of bottromycin stems from its unprecedented macrocyclic amidine rare β‐methylated amino acid residues. N ‐terminus precursor (BtmD) converted into by tailoring enzymes encoded in the btm gene cluster. However, little was known about key transformations this pathway,...

The formation of benzoin (Ph-CHOH-CO-Ph) from two molecules benzaldehyde, catalyzed by 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide in methanol buffered with Et(3)N/Et(3)NH(+)Cl(-) has been studied. Initial-rate studies at various concentrations PhCHO (0.1-1.7 M) showed that the reaction is close to being first order PhCHO. Following deuteriomethanol, (1)H NMR spectroscopy allowed rate constants for all three kinetically significant steps be determined. These show are partially...

F. J. Leeper, Nat. Prod. Rep., 1989, 6, 171 DOI: 10.1039/NP9890600171

Two reagents have been synthesized for selective labeling of cell surface azidoglycans, an unusually stable version a dibenzo cyclooctyne (TMDIBO) and third-generation difluorinated (DIFO3). Both syntheses are efficient with minimal purification, the is under basic acidic conditions. Flow cytometric measurements azidosugar labeled cancer cells, in which these were linked to fluorophore Alexa Fluor 647, gave signal-to-background ratio up 35 TMDIBO as compared ≈10 DIFO3 ≈5 phosphine reagent....

Dynamic alterations in cell surface glycosylation occur numerous biological processes that involve cell-cell communication and migration. We report here imaging of live mice using double click chemistry. Cell glycans were metabolically labeled peracetylated azido-labeled N-acetylgalactosamine then reacted, the first reaction, with either a cyclooctyne, Huisgen [3 + 2] cycloaddition, or Staudinger phosphine, via ligation. The second reaction was [4 inverse electron demand Diels-Alder between...

Streptomycete bacteria are a rich source of antibacterial natural products. Increasing antibiotic resistance is global concern and novel classes potent antibiotics rare. Here we report the identification genetic manipulation gene cluster for cyclic antimicrobial peptide bottromycin in Streptomyces scabies. Bottromycin active towards multi-drug resistant bacteria, such as MRSA VRE, contains biologically unique macrocyclic amidine. The btm biosynthetic was identified by genome mining confirmed...

Summary Polyketides represent an important class of bioactive natural products with a broad range biological activities. We identified recently large trans ‐acyltransferase ( AT ) polyketide synthase gene cluster responsible for the biosynthesis antifungal, anti‐oomycete and antitumor haterumalide, oocydin A ooc ). Using genome sequencing comparative genomics, we show that is widespread within biocontrol phytopathogenic strains enterobacteria, S erratia D ickeya . The analysis in frame...

A series of derivatives a triazole analogue thiamine has been synthesised. When tested as inhibitors porcine pyruvate dehydrogenase, the benzoyl ester proved to be potent pyrophosphate (TPP) competitive inhibitors, with affinity most (Ki = 54 nM) almost matching TPP itself. antiplasmodials, showed modest activity (IC50 value >60 μM), except for 4'-N-benzyl derivative, which an IC50 in low micromolar range. This was not affected by increasing extracellular concentration culture medium any...

Thiamine is metabolized into the coenzyme thiamine diphosphate (ThDP). Interrupting utilization leads to disease states. Oxythiamine, a analogue, oxythiamine (OxThDP), which inhibits ThDP-dependent enzymes. Oxythiamine has been used validate as an anti-malarial drug target. However, high doses are needed in vivo because of its rapid clearance, and potency decreases dramatically with levels. We report herein cell-permeable analogues possessing triazole ring hydroxamate tail replacing...