Ab initio (UHF/6-31G*) and density functional (Becke3LYP/D95*) calculations have been used to investigate the structures stabilities of radical cations DNA bases base pairs. The calculated pairs show excellent agreement with crystallographic data. most easily oxidizable base, guanine, forms a particularly stable cation pair cytosine, so that adiabatic ionization potential for guanine−cytosine hydrogen-bonded complex is about 0.75 eV lower than guanine itself. UBecke3LYP/D95*//UHF/6-31G*...

Seaweeds emerge as promising third-generation renewable for sustainable bioproduction. In the present work, we valorized brown seaweed to produce l-lysine, world's leading feed amino acid, using Corynebacterium glutamicum, which was streamlined by systems metabolic engineering. The mutant C. glutamicum SEA-1 served a starting point development because it produced small amounts of l-lysine from mannitol, major sugar, deletion its arabitol repressor AtlR and engineered pathway. Starting SEA-1,...

Time-resolved FTIR spectroscopic studies of the flash photolysis several 1-(2-nitrophenyl)ethyl ethers derived from aliphatic alcohols showed that a long-lived hemiacetal intermediate was formed during reaction. Breakdown this rate-limiting for product release. One these compounds (methyl 2-[1-(2-nitrophenyl)ethoxy]ethyl phosphate, 9) studied in detail by combination time-resolved and UV−vis spectroscopy. In addition, confirmed clean photolytic decomposition to expected alcohol,...

Most bacterial cytochrome P450 monooxygenases (P450s or CYPs) require two redox partner proteins for activity. To reduce complexity of the chain, Bacillus subtilis flavodoxin YkuN (Y) was fused to Escherichia coli reductase Fpr (R), and activity tuned by placing flexible (GGGGS)n rigid ([E/L]PPPP)n linkers (n = 1-5) in between. P-linker constructs typically outperformed their G-linker counterparts, with superior performance YR-P5, which carries linker ([E/L]PPPP)5. Molecular dynamics...

The suitability of decision trees in comparison to support vector machines for the classification chemical compounds into drugs and nondrugs was investigated. To account requirements upon screening virtual compound libraries, schemes successive filtering steps with gradual increasing computational cost are outlined. obtained prediction accuracy similar between machine approaches applied data sets. By using rapidly computable variables such as druglikeness indices, XlogP, molar refractivity,...

Natural redox partners of bacterial cytochrome P450s (P450s) are mostly unknown. Therefore, substrate conversions performed with heterologous partners; in the case CYP106A2 from Bacillus megaterium ATCC 13368, bovine adrenodoxin (Adx) and reductase (AdR). Our aim was to optimize system for improved product formation by testing 11 different combinations partners. We found that electron transfer protein 1(516-618) showed highest yield main product, 15β-hydroxyprogesterone, and, furthermore,...

Abstract Classification algorithms suffer from the curse of dimensionality, which leads to overfitting, particularly if problem is over‐determined. Therefore it particular interest identify most relevant descriptors reduce complexity. We applied Bayesian estimates model probability distribution values used for binary classification using n ‐fold cross‐validation. As a measure discriminative power classifiers, symmetric form Kullback–Leibler divergence their distributions was computed. found...

Abstract Cytochrome P450s are very versatile enzymes with great potential for biotechnological applications because of their ability to oxidize unactivated CH bonds. CYP105A1 from Streptomyces griseolus was first described as a herbicide‐inducible sulfonylurea hydroxylase, but it is also able convert other substrates such vitamin D 3 . To extend the substrate pool this interesting enzyme further, we screened small diterpenoid compound library and were show conversion several resin acids....

The production of regio- and stereoselectively hydroxylated steroids is high pharmaceutical interest can be achieved by cytochrome P450-based biocatalysts. CYP260A1 from Sorangium cellulosum strain So ce56 catalyzes hydroxylation C19 or C21 at the very unique 1α-position. However, conversion progesterone (PROG) unselective. In order to improve its selectivity we applied a semirational protein engineering approach, resulting in two different, highly stereoselective mutants replacing single...

Enzymes of the cytochrome P450 monooxygenase family 4 (CYP4) in mammals are generally involved either endobiotic metabolism (e.g., acting on fatty acids or eicosanoids), modification xenobiotics including therapeutic drugs. CYP4B1 is special, as it an enigmatic enzyme at interface between xenobiotic and metabolism. However, a systematic analysis CYP4B1’s substrate scope has not yet been reported. Herein, three-step approach to identify novel substrates for three orthologs (namely from...

Ab initio and other computational studies of bacterial reaction center cofactors are usually performed using the observed (low-resolution) X-ray structures. Unfortunately, these geometries necessarily approximate this can have dramatic influences on calculated properties. For example, energies four bacteriochlorophylls in Rhodobacter sphaeroides vary by over 160 kcal mol-1. To overcome problem, a combined quantum mechanical/molecular mechanical (QM/MM) method is employed to optimize...

Magnesium parameters for use with the semiempirical AM1 method are developed using a specially designed genetic algorithm. Parametrization priorities included development of robust parametrization capable describing wide range properties in diverse chemical environments, emphasis on structural features biologically relevant systems, e.g., chlorophylls. Specifically, test data set selection heats formation, geometric properties, dipole moment, and ionization energies evaluated 32 compounds...

Site-directed mutagenesis has been employed by a number of groups to produce mutants bacterial photosynthetic reaction centers, with the aim tuning their operation modifying hydrogen-bond patterns in close vicinity "special pair" bacteriochlorophylls P ≡ PLPM. Direct X-ray structural measurements consequences mutation are rare. Attention mostly focused on effects properties such as carbonyl stretching frequencies and midpoint potentials infer indirectly induced modifications. In this work,...

Abstract To predict the ability of drug‐like molecules to penetrate Central Nervous System (CNS), a decision tree was generated. This algorithm designed make straight forward yes/no about permeability blood‐brain barrier for given substance, based on numerical criteria large variety molecular descriptors. The achieved prediction accuracy 96% 186 compounds training set and 84% test comprising 38 molecules. We found that CNS+drugs are predicted with higher (>94%) than CNS‐ substances (>89%).

Variations of substituents at 2-substituted 4-azidopyrimidines allowed us to shift the azido–tetrazole equilibrium either two constitutional isomers. This can be exploited for click chemistry and fragment-based drug design.