Evidence for the existence of metallocarbohedrenes [MacI2 (M = Ti and V)] as a general class of stable neutral molecular clusters is reported. Studies of the formation and growth of metal-carbon clusters M,C, reveal the general mechanisms responsible for the formation of the prominent cagelike structure, M6C12, using a laser-based timeof-flight mass spectrometer. Investigation of the effect of the ionizing laser fluence over at least 4 orders of magnitude and studies at 1064, 532, 355, and 266 nm establish that the prominence of the M6CI2 cluster arises due to its presence as a neutral rather than as the photofragment of clusters of large size. The unusual stability of this species for both Ti and V is consistent with the proposed cagelike structure being a pentagonal dodecahedron (point group symmetry Th).
Although a wide variety of proteins can assemble into amyloid fibrils, the structure of the early oligomeric species on the aggregation pathways remains unknown at an atomic level of detail. In this paper we report, using molecular dynamics simulations with the OPEP coarse-grained force field, the free energy landscape of a tetramer and a heptamer of the beta2-microglobulin NHVTLSQ peptide. On the basis of a total of more than 17 ns trajectories started from various states, we find that both species are in equilibrium between amorphous and well-ordered aggregates with cross-beta-structure, a perpendicular bilayer beta-sheet, and, for the heptamer, six- or seven-stranded closed and open beta-barrels. Moreover, analysis of the heptamer trajectories shows that the perpendicular bilayer beta-sheet is one possible precursor of the beta-barrel, but that this barrel can also be formed from a twisted monolayer beta-sheet with successive addition of chains. Comparison with previous aggregation simulations and the fact that nature constructs transmembrane beta-sheet proteins with pores open the possibility that beta-barrels with small inner diameters may represent a common intermediate during the early steps of aggregation.
The preparation of α-functionalized organic acids can be greatly simplified by adopting a protocol involving the catalytic assembly of achiral building blocks. However, the enzymatic assembly of small amino acids and aldehydes to form numerous α-functionalized organic acids is highly desired and remains a significant challenge. Herein, we report an artificially designed chiral-group-resetting biocatalytic process, which uses simple achiral glycine and aldehydes to synthesize stereodefined α-functionalized organic acids. This cascade biocatalysis comprises a basic module and three different extender modules and operates in a modular assembly manner. The engineered Escherichia coli catalysts, which contained different module(s), provide access to α-keto acids, α-hydroxy acids, and α-amino acids with excellent conversion and enantioselectivities. Therefore, this biocatalytic process provides an attractive strategy for the conversion of low-cost achiral starting materials to high-value α-functionalized organic acids.
Threonine deaminase (TD, EC 4.3.1.19) mediates α,βelimination (deamination), which has untapped potential in the synthesis of unnatural α-keto acids. However, the narrow substrate scope of wild-type TD limits its application. This issue could be overcome by engineering the substrate tunnel of the enzyme. Here, Corynebacterium glutamicum TD (CgTD) was used as a model, and its substrate tunnel was identified as a gating element. On the basis of the gating characteristics and constitution of the substrate access tunnel of CgTD, an "open-gate" strategy was developed to improve its substrate scope toward bulky substrates. The best variant obtained following this approach, CgTD Mu7 , exhibited 90.6-fold greater catalytic efficiency (k cat / K M ) toward a bulky substrate such as phenylserine. The improvement was due to more efficient substrate coupling, deprotonation, and imine hydrolysis. CgTD Mu7 was used for efficient production of both natural and unnatural α-keto acids, including 2-oxobutyric acid (83.4 g L −1 , 99% conversion), phenylpyruvic acid (72.5 g L −1 , 95% conversion), 2-oxovaleric acid (21.1 g L −1 , 91% conversion), and 2-oxo-4-phenylbutyric acid (29.9 g L −1 , 84% conversion). The proposed strategy provides a theoretical basis for the synthesis of α-keto acids and is also effective for engineering other similar enzymes.
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