Search

UCS1025A is a fungal polyketide/alkaloid that displays strong inhibition of telomerase. The structures of UCS1025A and related natural products are featured by a tricyclic furopyrrolizidine connected to a trans-decalin fragment. We mined the genome of a thermophilic fungus and activated the ucs gene cluster to produce UCS1025A at a high titer. Genetic and biochemical analysis revealed a PKS-NRPS assembly line that activates 2S,3S-methylproline derived from L-isoleucine, followed by Knoevenagel condensation to construct the pyrrolizidine moiety. Oxidation of the 3S-methyl group to a carboxylate leads to an oxa-Michael cyclization and furnishes the furopyrrolizidine. Our work reveals a new strategy used by nature to construct heterocyclic alkaloid-like ring systems using assembly line logic. [ABSTRACT FROM AUTHOR]

Macrophorins are representative examples of isoprenoid epoxycyclohexenones containing cyclized drimane moieties. We located and characterized the biosynthetic gene cluster of macrophorin from Penicillium terrestris. MacJ encoded by this cluster was characterized to be the first example of a membrane-bound type-II terpene cyclase catalyzing the cyclization of meroterpenoids via direct protonation of the terminal olefinic bond in acyclic yanuthones. The late-stage functionalization and substrate promiscuity of MacJ make it a potential biocatalyst for the synthesis of macrophorin analogues. [ABSTRACT FROM AUTHOR]

Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity, and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this Review, we examine the different strategies used by nature to create new intra(inter)molecular bonds via redox chemistry. This Review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG-dependent oxygenases, and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installations of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of "disappearing" reactive handles. Last, oxidative rearrangement of rings systems, including contractions and expansions, will be covered. [ABSTRACT FROM AUTHOR]

Highly connected crystalline porous materials are rare but promising for gas adsorption and separation since varying pore shape and size as well as high framework stability may be achieved by tuning the framework connectivity. We demonstrate herein two highly connected frameworks, namely, {[Cd7(BDC)6(MTAZ)2(DMF)6].3DMF}n (SNNU-11) and {[Cd5(BDC) (PTAZ)8(DMF)2].4DMF}n (SNNU-12) (BDC = 1,4-benzenedicarboxylic acid, MTAZ = 5-methyl-tetrazole, and PTAZ = 5-(4-pyridyl)-tetrazole). In SNNU-11, BDC ligands link S-shaped [Cd7(MTAZ)2] motifs to form a novel 10-connected framework, which is related to but different from the reported 10-connected bct and gpu nets. Under the similar synthesis condition, the utilization of 5-(4-pyridyl)-tetrazole produced SNNU-12, which is constructed from zigzag Cd5 clusters and exhibits a 12-connected fcu net. Notably, SNNU-12 decorated with uncoordinated nitrogen sites shows not only high CO2 uptake capacity (87.9 cm3 g-1, 1 atm, and 273 K) but also high CO2 over CH4 and C2 hydrocarbons over CH4 selectivity, which is among the highest values of highly connected MOF materials (connectivity ≥10) including famous UiO-66 and rare-earth fcu-MOFs under the same temperature and pressure. [ABSTRACT FROM AUTHOR]

The structural diversity and biological activities of fungal indole diterpenes (IDTs) are generated in large part by the IDT cyclases (IDTCs). Identifying different IDTCs from IDT biosynthetic pathways is therefore important toward understanding how these enzymes introduce chemical diversity from a common linear precursor. However, IDTCs involved in the cyclization of the well-known aflavinine subgroup of IDTs have not been discovered. Here, using Saccharomyces cerevisiae as a heterologous host and a phylogenetically guided enzyme mining approach, we combinatorially assembled IDT biosynthetic pathways using IDTCs homologues identified from different fungal hosts. We identified the genetically standalone IDTCs involved in the cyclization of aflavinine and anominine and produced new IDTs not previously isolated. The cyclization mechanisms of the new IDTCs were proposed based on the yeast reconstitution results. Our studies demonstrate heterologous pathway assembly is a useful tool in the reconstitution of unclustered biosynthetic pathways. [ABSTRACT FROM AUTHOR]

Modular polyketide synthases (PKSs) are well known to use ketosynthase (KS)-driven carbon-carbon bond formation, dehydratase-mediated dehydration to form double bonds, and product release by thioesterase (TE), all of which are regarded as the "canonical" roles for most polyketide biosyntheses. FR901464 is biosynthesized by a complex acyltransferase-less PKS system involving a nonterminal TE domain and several mutated KS domains. Here we demonstrate that this TE catalyzes the dehydration of the polyketide intermediate to yield a cis-double bond and a mutated KS transfers the nascent polyketide chain with only a cis-double bond to the downstream acyl carrier protein. These findings not only provide new insights into different enzymatic functions of PKS domains but also suggest an alternative strategy for cis-double bond formation during the polyketide assembly line. [ABSTRACT FROM AUTHOR]

We report that a 2,2′:6′,2″-terpyridylmacrocycle-Ni complex can efficiently mediate the threading of two alkyl chains with bulky end groups in an active metal template sp3-carbon-to-sp3-carbon homocoupling reaction, resulting in a rare example of a doubly threaded [3]rotaxane in up to 51% yield. The unusual architecture is confirmed by X-ray crystallography (the first time that a one-ring-two-thread [3]rotaxane has been characterized in the solid state) and is found to be stable with respect to dethreading despite the large ring size of the macrocycle. Through such active template reactions, in principle, a macrocycle should be able to assemble as many axles in its cavity as the size of the ring and the stoppers will allow. A general method for threading multiple axles through a macrocycle adds significantly to the tools available for the synthesis of different types of rotaxane architectures. [ABSTRACT FROM AUTHOR]

Treatment of the o-hydroxyaryl imidazolinium pro-ligands (2-OH-3,5-tBu2C6H2)(R)(C3H3N2)−[R = iPr (1a), tBu (1b), Ph (1c), Mes (1d)] with NiL2Cl2(L = PPh3, Py) or Ni(OAc)2·4H2O afforded the corresponding cisbis(aryloxide-NHC) nickel complexes 2−5. Notably, the products were independent from the pro-ligands/Ni ratios. The same complexes were obtained with the pro-ligands/Ni ratio of 1:1 or 2:1. All the complexes were characterized by 1H and 13C NMR, high-resolution mass spectrometry (HRMS), and elemental analysis. The molecular structures of the aryloxide-NHC-ligated nickel complexes 2−5were determined by single-crystal X-ray diffraction analysis. With methylaluminoxane (MAO) as cocatalyst, the nickel complexes showed moderate catalytic activities (106g of PNB (mol of Ni)−1h−1) in the addition polymerization of norbornene. [ABSTRACT FROM AUTHOR]

This work reports the results of a thermodynamic investigation of the ternary CsCl−MgCl2−H2O mixed electrolyte system. The activity coefficients of this mixed aqueous electrolyte system have been studied with the electromotive force (EMF) measurement of the cell: Cs ion-selective electrode (ISE)|CsCl (mA), MgCl2(mB), H2O|Ag/AgCl at 298.15 K and over total ionic strengths from (0.01 to 1.50) mol·kg−1for different ionic strength fractions yBof MgCl2with yB= 0, 0.25, 0.50, and 0.75. The cesium ion-selective electrode (Cs-ISE) and the Ag/AgCl electrode used in this work were made in this laboratory and had a good Nernstian response. The experimental results obey the Harned rule, and the Pitzer model can be used to describe this aqueous system satisfactorily. The osmotic coefficients, excess Gibbs energies, and activities of water of the mixtures were also calculated. [ABSTRACT FROM AUTHOR]

β-Carboline (βC) alkaloids constitute a large family of indole alkaloids that exhibit diverse pharmacological properties, such as antitumor, antiviral, antiparasitic, and antimicrobial activities. Here, we report that a flavoprotein StnP2 catalyzes the dehydrogenation at C1-N2 of a tetrahydro-β-carboline (THβC) generating a 3,4-dihydro-β-carboline (DHβC), and the DHβC subsequently undergoes a spontaneous dehydrogenation to βC formation involved in the biosynthesis of the antitumor agent streptonigrin. Biochemical characterization showed that StnP2 catalyzed the highly regio- and stereo-selective dehydrogenation, and StnP2 exhibits promiscuity toward different THβCs. This study provides an alternative kind of enzyme catalyzing the biosynthesis of βC alkaloids and enhances the importance of flavoproteins.

High storage capacity, high separation selectivity, and high structure stability are essential for an idea gas adsorbent. However, it is not easy to achieve all three at the same time, even for the promising metal-organic framework (MOF) adsorbents. We demonstrate herein that robust [Sc 3 O]-organic frameworks could be regulated by a micropore combination strategy for high-performance acetylene adsorption. Under the same solvent system with formic acid as a modulator, similar tritopic ligands extend [Sc 3 O(COO) 6 ] trigonal-prismatic clusters to generate SNNU-5-Sc and SNNU-150-Sc adsorbents. Notably, the two Sc-MOFs can keep their architectures over 24 h in water at different pH values (2-12) or at 90 °C. Modulated by the linker symmetry, the final stacking metal-organic polyhedral cages produce open window sizes of about 10 Å for SNNU-5-Sc and 5 Å + 7 Å for SNNU-150-Sc. Due to such micropore combinations, SNNU-5-Sc exhibits a top-level C 2 H 2 uptake of 211.2 cm 3 g -1 (1 atm and 273 K) and SNNU-150-Sc shows high C 2 H 2 /CH 4 , C 2 H 2 /C 2 H 4 , and C 2 H 2 /CO 2 selectivities of 80.65, 4.03, and 8.19, respectively, under ambient conditions. Dynamic breakthrough curves obtained on a fixed-bed column and grand canonical Monte Carlo (GCMC) simulations further support their prominent acetylene storage and purification performance. High framework stability, storage capacity, and separation selectivity make SNNU-5-Sc and SNNU-150-Sc ideal acetylene adsorbents in practical applications.

The flavoprotein monooxygenase (FPMO) TerC is encoded by all known cyclopentene biosynthetic gene clusters. It can catalyze oxidative dearomatization toward a series of 6-HM analogues and further induces different skeletal distortions to form either benzoquinone or pyrone by bimodal reaction cascades, which is only governed by the C7 substitutions. Beyond our study demonstrated bimodal reaction cascades and advanced the biosynthetic knowledge of fungal cyclopentenes, this work also sets the stage for the bioengineering of 6-HM polyketides.

A genome-directed discovery strategy to identify new tetrahydroisoquinolines (THIQs) was applied to deep-sea derived Streptomyces niveus SCSIO 3406; 11 THIQs were found representing three THIQ classes. Known aclidinomycins A ( 1 ) and B ( 2 ) were isolated along with nine new compounds, aclidinomycins C-K ( 3 - 11 ). The structures were elucidated using extensive spectroscopic analyses and single-crystal X-ray diffraction methods. The core skeleton of compounds 6 - 9 contains a fused tetrahydropyran (THP) as an integral part of a distinct type of 6/6/6/6/5/5 polycyclic motif. This is the first report of such a system. Beyond their discovery, we also report here a proposed biosynthetic route to these interesting natural products as well as a preliminary survey of their antimicrobial activities.

Hirsutellones are fungal natural products containing a macrocyclic para- cyclophane connected to a decahydrofluorene ring system. We have elucidated the biosynthetic pathway for pyrrocidine B ( 3 ) and GKK1032 A 2 ( 4 ). Two small hypothetical proteins, an oxidoreductase and a lipocalin-like protein, function cooperatively in the oxidative cyclization of the cyclophane, while an additional hypothetical protein in the pyrrocidine pathway catalyzes the exo- specific cycloaddition to form the cis- fused decahydrofluorene.

The construction of superstable metal-organic frameworks (MOFs) for selective gas uptake is urgently demanded but remains a great challenge. Herein, a unique bifunctional deformed [Ga 3 O(COO) 6 ] inorganic secondary building unit (SBU) generated from the desymmetrical evolution of typical triangular prismatic trinuclear cluster was first introduced, which was extended by an isosceles triangular organic linker to produce a robust Ga-MOF ( SNNU-63 ). Remarkably, SNNU-63 can stabilize in water at 25 °C for 96 h and at 80 °C for more than 24 h, which surpasses nearly all other Ga-MOFs. The combined effects of open metal sites and hydrophobic pore environment provided by deformed [Ga 3 O] SBUs render SNNU-63 with high C 2 H 2 storage capacity and efficient C 2 H 2 and natural gas purification performance. The ideal adsorbed solution theory calculation, column breakthrough tests, and grand canonical Monte Carlo simulations demonstrate that SNNU-63 is a potential material for addressing the challenge of C 2 H 2 /CO 2 and C 2 H 2 /CH 4 mixture separation under ambient conditions.