5 research outputs found
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 IC<sub>50</sub> 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