Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids

Abstract

Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity.H erein, the identification of bacterial PAsf rom entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve an on-ribosomal peptide synthetase.T he occurrence of these biosynthesis gene clusters in Gram-negative and Gram-positive bacteria indicates an important biological function in bacteria. Figure 3. Proposed biosynthesis of bacterial PA and LCC compounds.S tandard NRPS biochemical pathways (A) might be followed by TE-catalyzed dehydration and cyclization (B) prior to the enzymatic cascade catalyzed by PxaB.

The benzodiazepine-like natural product tilivalline is produced by the entomopathogenic bacterium Xenorhabdus eapokensis

“…For its construction yeast homologous recombination (ExRec) cloning was used [ 53 ]. Therefore, the shuttle vector pCX2 (genotype: 2μ ori, pBR322 ori, G418 R , Kan R , pBAD promoter [ 54 ]), was linearized by Sac I. Next, the TV BGC was amplified by PCR using gDNA from X. indica using the oligonucleotides HW p037 for and HW p038 rev ( , , respectively); letters in italic indicate homologous regions of insert to the pCX2 shuttle vector.…”

The Enzymology of Organic Transformations: A Survey of Name Reactions in Biological Systems

“…A similar biosynthetic route has also been proposed for the formation of pyrrolizixenamides in Xenorhabdus stockiae. [167] 4.1.3. Cytochrome P450 BVMO Although the BVMOs described above are all flavindependent, several cytochrome P450 enzymes that catalyze Baeyer-Villiger reactions have also been identified.…”

Discovery and Biosynthesis of Azabicyclene, a Conserved Nonribosomal Peptide in Pseudomonas aeruginosa

“…Homologues of AzeB and AzeC were identified in the biosynthetic gene clusters for legonmycins and brabantamides. 17,[23][24][25] Our work marks the first in vitro reconstitution of the class of NRPSs in pyrrolizidine alkaloid biosynthesis and provides biochemical evidence that the NRPS AzeB is essential and sufficient for synthesizing pyridinones. Conversion of L-Ser-L-AZC or L-Ser-L-Pro dipeptide to pyridinones likely entails a 2,3-dehydration of the L-Ser side chain followed by a cyclization (Figure S19).…”