α-Vinylic amino acids: occurrence, asymmetric synthesis, and biochemical mechanisms

Abstract

This report presents an overview of the family of naturally occurring 'vinylic' amino acids, namely those that feature a C-C double bond directly attached to the α-carbon, along the side chain. Strategies that have been brought to bear on the stereocontrolled synthesis of these olefinic amino acids are surveyed. The mechanistic diversity by which such 'vinylic triggers' can be actuated in a PLP (pyridoxal phosphate) enzyme active site is then highlighted by discussions of vinylglycine (VG), its substituted congeners, particularly AVG [4E-(2'-aminoethoxy)vinylglycine], and a naturally occurring VG-progenitor, SMM (S-methylmethionine).

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

“… § Jill M. Sturdivant was previously published under the name Jill M. McFadden 36b,38b–d for research conducted in these laboratories. …”

The Pseudomonas aeruginosa antimetabolite L -2-amino-4-methoxy-trans-3-butenoic acid (AMB) is made from glutamate and two alanine residues via a thiotemplate-linked tripeptide precursor

“…As previously mentioned, AMB inhibits PLP-dependent enzymes (Berkowitz et al, 2006) and as such could act as a growth inhibitor in the producer as well. We thus speculate that the two flanking L -Ala residues could not only act as protective groups during the conversion of L -Glu to AMB, but also have the additional function of preventing AMB toxicity during biosynthesis.…”

“…One of the many toxins that this bacterium produces is L -2-amino-4-methoxy- trans -3-butenoic acid (AMB), a non-proteinogenic amino acid belonging to a small group of natural compounds known as oxyvinylglycines (Berkowitz et al, 2006). Other members of this group are aminoethoxyvinylglycine (AVG), dimethyliminooxyvinylglycine, and guanidinooxyvinylglycine from Streptomyces spp.…”

“…(Pruess et al, 1974; Hirata et al, 1993), rhizobitoxin made by Bradyrhizobium japonicum and P. andropogonis (Owens et al, 1972; Mitchell et al, 1986), as well as the recently identified 4-formylaminooxyvinylglycine (FVG) isolated from P. fluorescens WH6 (McPhail et al, 2010). Oxyvinylglycines irreversibly inhibit pyridoxal phosphate (PLP)-dependent enzymes and thus have multiple targets in bacteria, animals, and plants (Berkowitz et al, 2006). A prominent plant target is the ethylene biosynthesis enzyme ACC synthase, which is inhibited by AVG.…”

Crystallization and preliminary X-ray crystallographic analysis of a putative nonribosomal peptide synthase AmbB fromPseudomonas aeruginosa

“…l-2-Amino-4-methoxy-trans-3-butenoic acid (AMB; methoxyvinylglycine) is a secondary metabolite which is thought to be a potent antibiotic (Sahm et al, 1973;Scannel et al, 1972;Tisdale, 1980;Berkowitz et al, 2006). A five-gene cluster ambABCDE has been identified as being involved in AMB biosynthesis and exportation using biochemical assays combined with site-directed mutagenesis in strain PAO of P. aeruginosa (Lee et al, 2010).…”