l-Proline rubidium salt catalyzes the asymmetric Michael addition of malonate anions to prochiral enones and enals. This method can be applied to a wide range of substrates to give adducts with a predictable absolute configuration:  (S)-adducts from (E)-enones/enals and (R)-adducts from cyclic (Z)-enones. Both the secondary amine moiety and the carboxylate moiety are critical for the catalytic activity and asymmetric induction. Varying the countercation also affects the reaction course. High enantiomeric excesses were attained when di(tert-butyl) malonate was added to (E)-enones in the presence of CsF. The stereochemistry of the Michael reaction indicates that asymmetric induction takes place via enantioface discrimination involving the acceptor α-carbon atom rather than the β-carbon atom.

Amino-group carrier proteins (AmCPs) mediate the biosynthesis of lysine and arginine in some bacteria and archaea. Here we demonstrate that an uncharacterized AmCP-mediated biosynthetic system functions to biosynthesize the previously uncharacterized and nonproteinogenic amino acid (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH) in Streptomyces sp. SANK 60404. DADH is incorporated into a novel peptide metabolite, vazabitide A, featuring an azabicyclo-ring structure, by nonribosomal peptide synthetases and successive modification enzymes in this bacterium. As the AmCP-mediated machinery for DADH biosynthesis is widely distributed in bacteria, further analysis of uncharacterized AmCP-containing gene clusters will lead to the discovery of novel bioactive compounds and novel biosynthetic enzymes.

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Distinct progress has been made in the catalytic asymmetric Michael addition of prochiral enolates to acceptors for example, enantioselective addition of indane-I-one-2-carboxylate to methyl vinyl ketone."I These reactions rely on the differentiation of donor enantiofaces by chiral catalysts. In contrast, very little success has been achieved in the enantioselective Michael addition of an enolate to prochiral acceptors, despite the high potential of this reaction to produce various chiral carbon centers."' The conventional methods appear to be highly substrate specific, and enantiomeric excesses attained have generally not been high. We disclose herein the first catalytic asymmetric Michael addition of a simple malonate ion to prochiral enones and enals, which employs the readily available rubidium salt of L-proline @).I3' The optical yields are substantial for this type of reaction, and the method can be applied to a range of acceptors to give adducts of predictable absolute configurations.The Michael addition of dimethyl malonate in methanol catalyzed by the lithium salt of L-proline gave race mate^.[^^ However, appreciable asymmetric inductions were observed when the reactions were carried out in chloroform. Furthermore, the rubidium salt 215] was found to possess remarkably high catalytic activity compared with the lithium salt, and higher optical yields were attained with diisopropyl ester lr6] (Scheme 1). Enantioselectivities up to 77% ee were

Fosfomycin is a wide-spectrum phosphonate antibiotic that is used clinically to treat cystitis, tympanitis, etc. Its biosynthesis starts with the formation of a carbon-phosphorus bond catalyzed by the phosphoenolpyruvate phosphomutase Fom1. We identified an additional cytidylyltransferase (CyTase) domain at the Fom1 N-terminus in addition to the phosphoenolpyruvate phosphomutase domain at the Fom1 C-terminus. Here, we demonstrate that Fom1 is bifunctional and that the Fom1 CyTase domain catalyzes the cytidylylation of the 2-hydroxyethylphosphonate (HEP) intermediate to produce cytidylyl-HEP. On the basis of this new function of Fom1, we propose a revised fosfomycin biosynthetic pathway that involves the transient CMP-conjugated intermediate. The identification of a biosynthetic mechanism via such transient cytidylylation of a biosynthetic intermediate fundamentally advances the understanding of phosphonate biosynthesis in nature. The crystal structure of the cytidylyl-HEP-bound CyTase domain provides a basis for the substrate specificity and reveals unique catalytic elements not found in other members of the CyTase family.