Symmetric Grothendieck polynomials, skew Cauchy identities, and dual filtered Young graphs

Symmetric Grothendieck polynomials are analogues of Schur polynomials in the K-theory of Grassmannians. We build dual families of symmetric Grothendieck polynomials using Schur operators. With this approach we prove skew Cauchy identity and then derive various applications: skew Pieri rules, dual filtrations of Young's lattice, generating series and enumerative identities. We also give a new explanation of the finite expansion property for products of Grothendieck polynomials

Antibacterial Muraymycins from Mutant Strains of <i>Streptomyces</i> sp. NRRL 30471

Muraymycins are nucleoside antibiotics isolated from <i>Streptomyces</i> sp. NRRL 30471 and several mutant strains thereof that were generated by random, chemical mutagenesis. Reinvestigation of two mutant strains using new media conditions led to the isolation of three new muraymycin congeners, named B8, B9, and C6 (<b>1</b>–<b>3</b>), as well as a known muraymycin, C1. Structures of the compounds were elucidated by HRMS and 1D and 2D NMR spectroscopic analyses. Complete 2D NMR assignments for the known muraymycin C1 are also provided for the first time. Compounds <b>1</b> and <b>2</b>, which differ from other muraymycins by having an elongated, terminally branched fatty acid side chain, had picomolar IC₅₀ values against <i>Staphylococcus aureus</i> and <i>Aquifex aeolicus</i> MraY and showed good antibacterial activity against <i>S. aureus</i> (MIC = 2 and 6 μg/mL, respectively) and <i>Escherichia coli</i> Δ<i>tolC</i> (MIC = 4 and 2 μg/mL, respectively). Compound <b>3</b>, which is characterized by an <i>N</i>-acetyl modification of the primary amine of the dissacharide core that is shared among nearly all of the reported muraymycin congeners, greatly reduced its inhibitory and antibacterial activity compared to nonacylated muraymycin C1, which possibly indicates this modification is used for self-resistance

Crotonase Catalysis Enables Flexible Production of Functionalized Prolines and Carbapenams

The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers

Crotonase Catalysis Enables Flexible Production of Functionalized Prolines and Carbapenams

The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers

Amalgamation of Nucleosides and Amino Acids in Antibiotic Biosynthesis: Discovery of an l‑Threonine:Uridine-5′-Aldehyde Transaldolase

The lipopeptidyl nucleoside antibiotics represented by A-90289, caprazamycin, and muraymycin are structurally highlighted by a nucleoside core that contains a nonproteinogenic β-hydroxy-α-amino acid named 5′-C-glycyluridine (GlyU). Bioinformatic analysis of the biosynthetic gene clusters revealed a shared open reading frame encoding a protein with sequence similarity to serine hydroxymethyltransferases, resulting in the proposal that this shared enzyme catalyzes an aldol-type condensation with glycine and uridine-5′-aldehyde to furnish GlyU. Using LipK involved in A-90289 biosynthesis as a model, we now functionally assign and characterize the enzyme responsible for the C–C bond-forming event during GlyU biosynthesis as an l-threonine:uridine-5′-aldehyde transaldolase. Biochemical analysis revealed this transformation is dependent upon pyridoxal-5′-phosphate, the enzyme has no activity with alternative amino acids, such as glycine or serine, as aldol donors, and acetaldehyde is a coproduct. Structural characterization of the enzyme product is consistent with stereochemical assignment as the <i>threo</i> diastereomer (5′<i>S</i>,6′<i>S</i>)-GlyU. Thus this enzyme orchestrates C–C bond breaking and formation with concomitant installation of two stereocenters to make a new l-α-amino acid with a nucleoside side chain