38335-24-9Relevant articles and documents
β-Lactone formation during product release from a nonribosomal peptide synthetase
Schaffer, Jason E,Reck, Margaret R,Prasad, Neha K,Wencewicz, Timothy A
, p. 737 - 744 (2017/06/27)
Nonribosomal peptide synthetases (NRPSs) are multidomain modular biosynthetic assembly lines that polymerize amino acids into a myriad of biologically active nonribosomal peptides (NRPs). NRPS thioesterase (TE) domains employ diverse release strategies for off-loading thioester-tethered polymeric peptides from termination modules typically via hydrolysis, aminolysis, or cyclization to provide mature antibiotics as carboxylic acids/esters, amides, and lactams/lactones, respectively. Here we report the enzyme-catalyzed formation of a highly strained β-lactone ring during TE-mediated cyclization of a β-hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly line. The Obi NRPS (ObiF) contains a type I TE domain with a rare catalytic cysteine residue that plays a direct role in β-lactone ring formation. We present a detailed genetic and biochemical characterization of the entire Obi biosynthetic gene cluster in plant-associated Pseudomonas fluorescens ATCC 39502 that establishes a general strategy for β-lactone biogenesis.
Deracemization and Stereoinversion of α-Amino Acids by l-Amino Acid Deaminase
Rosini, Elena,Melis, Roberta,Molla, Gianluca,Tessaro, Davide,Pollegioni, Loredano
, p. 3773 - 3781 (2017/11/13)
Enantiomerically pure α-amino acids are compounds of primary interest for the fine chemical, pharmaceutical, and agrochemical sectors. Amino acid oxidases are used for resolving d,l-amino acids in biocatalysis. We recently demonstrated that l-amino acid deaminase from Proteus myxofaciens (PmaLAAD) shows peculiar features for biotechnological applications, such as a high production level as soluble protein in Escherichia coli and a stable binding with the flavin cofactor. Since l-amino acid deaminases are membrane-bound enzymes, previous applications were mainly based on the use of cell-based methods. Now, taking advantage of the broad substrate specificity of PmaLAAD, a number of natural and synthetic l-amino acids were fully converted by the purified enzyme into the corresponding α-keto acids: the fastest conversion was obtained for 4-nitrophenylalanine. Analogously, starting from racemic solutions, the full resolution (ee >99%) was also achieved. Notably, d,l-1-naphthylalanine was resolved either into the d- or the l-enantiomer by using PmaLAAD or the d-amino acid oxidase variant having a glycine at position 213, respectively, and was fully deracemized when the two enzymes were used jointly. Moreover, the complete stereoinversion of l-4-nitrophenylalanine was achieved using PmaLAAD and a small molar excess of borane tert-butylamine complex. Taken together, recombinant PmaLAAD represents an l-specific amino acid deaminase suitable for producing the pure enantiomers of several natural and synthetic amino acids or the corresponding keto acids, compounds of biotechnological or pharmaceutical relevance. (Figure presented.).
Reactions of Trialkylsilyl Trifluoromethanesulfonates XI. - Synthesis of α-Oxocarboxylic Acid Derivatives from 2-O-Functionalized Trimethylsilyl Ketene Acetals
Simchen, Gerhard,Siegl, Gerald
, p. 607 - 614 (2007/10/02)
The cyclic ketene acetals 3, 5 are prepared from the dioxolanone 2 resp. the oxazolidinediones 4 by silylation with trimethylsilyl triflate (1)/triethylamine.In an aldol addition/Peterson olefination reaction catalysed by 1 the ketene acetals 3, 5 yield the (E/Z)-benzylidene derivatives 7, 12, 13 in reaction with aromatic aldehydes 6.In a side reaction the α-(trimethylsilyl)benzylidene derivatives 8 are formed from 3 and 6.Compounds 7 can be hydrolysed to yield α-ketocarboxylic acids 14.The latter are also obtained via β-elimination of trimethylsilanol from 2,3-bis(trimethylsiloxy)carboxylic acid anhydride/DMAP/pyridine. Key Words: 1,3-Dioxolanes / 1,3-Oxazolidines / α-Oxocarboxylic acids
