Prenylation and Dehydrogenation of a C2-Reversely Prenylated Diketopiperazine as a Branching Point in the Biosynthesis of Echinulin Family Alkaloids in Aspergillus ruber

Author(s):  
Jonas Nies ◽  
Shu-Ming Li
Keyword(s):  
2021 ◽  
Vol 11 (9) ◽  
pp. 4048
Author(s):  
Javier A. Linares-Pastén ◽  
Lilja Björk Jonsdottir ◽  
Gudmundur O. Hreggvidsson ◽  
Olafur H. Fridjonsson ◽  
Hildegard Watzlawick ◽  
...  

The structures of glycoside hydrolase family 17 (GH17) catalytic modules from modular proteins in the ndvB loci in Pseudomonas aeruginosa (Glt1), P. putida (Glt3) and Bradyrhizobium diazoefficiens (previously B. japonicum) (Glt20) were modeled to shed light on reported differences between these homologous transglycosylases concerning substrate size, preferred cleavage site (from reducing end (Glt20: DP2 product) or non-reducing end (Glt1, Glt3: DP4 products)), branching (Glt20) and linkage formed (1,3-linkage in Glt1, Glt3 and 1,6-linkage in Glt20). Hybrid models were built and stability of the resulting TIM-barrel structures was supported by molecular dynamics simulations. Catalytic amino acids were identified by superimposition of GH17 structures, and function was verified by mutagenesis using Glt20 as template (i.e., E120 and E209). Ligand docking revealed six putative subsites (−4, −3, −2, −1, +1 and +2), and the conserved interacting residues suggest substrate binding in the same orientation in all three transglycosylases, despite release of the donor oligosaccharide product from either the reducing (Glt20) or non-reducing end (Glt1, Gl3). Subsites +1 and +2 are most conserved and the difference in release is likely due to changes in loop structures, leading to loss of hydrogen bonds in Glt20. Substrate docking in Glt20 indicate that presence of covalently bound donor in glycone subsites −4 to −1 creates space to accommodate acceptor oligosaccharide in alternative subsites in the catalytic cleft, promoting a branching point and formation of a 1,6-linkage. The minimum donor size of DP5, can be explained assuming preferred binding of DP4 substrates in subsite −4 to −1, preventing catalysis.


2015 ◽  
Vol 51 (18) ◽  
pp. 3797-3800 ◽  
Author(s):  
Nathalie Gatto ◽  
Abith Vattekkatte ◽  
Tobias Köllner ◽  
Jörg Degenhardt ◽  
Jonathan Gershenzon ◽  
...  

Deuterium surrounded carbocations support branching point analyses of multi product terpenoid synthases.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Reinis Rutkis ◽  
Inese Strazdina ◽  
Zane Lasa ◽  
Per Bruheim ◽  
Uldis Kalnenieks

Abstract Objective Zymomonas mobilis is an alpha-proteobacterium with a rapid ethanologenic pathway, involving Entner–Doudoroff (E–D) glycolysis, pyruvate decarboxylase (Pdc) and two alcohol dehydrogenase (ADH) isoenzymes. Pyruvate is the end-product of the E–D pathway and the substrate for Pdc. Construction and study of Pdc-deficient strains is of key importance for Z. mobilis metabolic engineering, because the pyruvate node represents the central branching point, most novel pathways divert from ethanol synthesis. In the present work, we examined the aerobic metabolism of a strain with partly inactivated Pdc. Results Relative to its parent strain the mutant produced more pyruvate. Yet, it also yielded more acetaldehyde, the product of the Pdc reaction and the substrate for ADH, although the bulk ADH activity was similar in both strains, while the Pdc activity in the mutant was reduced by half. Simulations with the kinetic model of Z. mobilis E-D pathway indicated that, for the observed acetaldehyde to ethanol production ratio in the mutant, the ratio between its respiratory NADH oxidase and ADH activities should be significantly higher, than the measured values. Implications of this finding for the directionality of the ADH isoenzyme operation in vivo and interactions between ADH and Pdc are discussed.


2017 ◽  
Vol 53 (74) ◽  
pp. 10255-10258 ◽  
Author(s):  
Qiang Liu ◽  
Hans. A. V. Kistemaker ◽  
Herman S. Overkleeft ◽  
Gijsbert A. van der Marel ◽  
Dmitri V. Filippov

Total synthesis provided the first independent confirmation of the chemical structure of the branching point in poly(ADP ribose).


2005 ◽  
Vol 37 (4) ◽  
pp. 1116-1146 ◽  
Author(s):  
Pierre Brémaud ◽  
Laurent Massoulié ◽  
Andrea Ridolfi

In this article, we review known results and present new ones concerning the power spectra of large classes of signals and random fields driven by an underlying point process, such as spatial shot noises (with random impulse response and arbitrary basic stationary point processes described by their Bartlett spectra) and signals or fields sampled at random times or points (where the sampling point process is again quite general). We also obtain the Bartlett spectrum for the general linear Hawkes spatial branching point process (with random fertility rate and general immigrant process described by its Bartlett spectrum). We then obtain the Bochner spectra of general spatial linear birth and death processes. Finally, we address the issues of random sampling and linear reconstruction of a signal from its random samples, reviewing and extending former results.


2017 ◽  
Author(s):  
Konstantin Gunbin ◽  
Konstantin Popadin ◽  
Leonid Peshkin ◽  
Sofia Annis ◽  
Rebecca Ackermann ◽  
...  

The question: human evolution- gradual process or a rapid discontinuous change? Whether human origin was a gradual process or a result of rapid change has been a focus of intense debate. Of particular interest is the climate change ~2.9-2.5 Ma, thought to have precipitated the separation of the genus Homo (~2.8Ma). The debate mostly concerned continuity/punctuality of the fossil record, but of course the rate of the underlying genetic change is of ultimate interest/importance. Did hominid lineage experience an increased mutation rate when a large number of hominins emerged and eventually gave rise to the split between Australopitecus/Paranthropus and Homo? The obstacle: vague timing of conventional mutations. The difficulty in answering the above question lies in the way past mutations are timed. Conventional point mutations are assigned to specific branches of the DNA-derived phylogenetic trees. The essence of the problem is that mutations can be located within branch segments from branching point to branching point, but the exact position within the segment is principally unknown. Because the hominid DNA-derived phylogenetic tree is rather sparsely populated with branches, the precision of mutation timing is low, e.g., human-specific mutations can be positioned within ~6 My from separation from chimpanzee. The solution: NUMTs – mutations with an internal clock. NUMTs are insertions of mtDNA sequences into the nuclear genome. Unlike point mutation, each NUMTs actually represents a branch on the mtDNA phylogenic tree and thus its time of insertion can be determined as precise as their branching point can be positioned on the tree. In a sense, NUMTs are “mutations with an internal clock”, which is synchronized with the well-established mtDNA mutation evolution clock. By determining the NUMTs’ insertion time points, one can ask whether whether NUMTs were inserted at a constant rate over time or at increased rate during critical periods of evolution, according with the “punctuated evolution” model. Results: Hundreds of pseudogenes have been inserted into the human genome over the last ~60 My of which we considered the last 6 My. Various quality filters resulted in the selection of 18 NUMTs most suitable for phylogenetic analysis. Insertion times of these 18 NUMTs cluster around 2.8Ma. While timing of insertion of NUMTs is imprecise, the observation such a cluster is highly statistically significant. Discussion: It is tempting to hypothesize that accelerated insertion of NUMTs is somehow linked to the speciation process. NUMTs could be either "riders i.e., the rate of insertion could be increased by the overall higher genome flexibility during the speciation period, or "drivers", i.e. they are fixed in the population at increased rate during speciation due to increased selective pressures. If correct, the hypothesis of accelerated pseudogenization would support the idea that evolution of our genus might have been discontinuous.


2018 ◽  
Vol 12 (2) ◽  
pp. 167-171 ◽  
Author(s):  
Ichiro Tonogai ◽  
Fumio Hayashi ◽  
Yoshihiro Tsuruo ◽  
Koichi Sairyo

Background. This study characterized the anterior medial malleolar artery (AMMA) branching from the anterior tibial artery (ATA) to identify problems in anterior ankle arthroscopy possibly contributing to injury to the AMMA. Methods. Barium was injected into 12 adult cadaveric feet via the external iliac artery and the origin and branching direction of the AMMA were identified on computed tomography. Results. The AMMA originated from the level of the ankle joint and below and above the ankle joint line (AJL) in 4 (33.3%), 6 (50.0%), and 1 (8.3%) specimen, respectively. Mean distance from the AJL to the branching point of the AMMA on the sagittal plane was 2.5 mm distal to the AJL. Mean angle between the distal longitudinal axis of the ATA and AMMA was 83.2°. Conclusions. This study established the origin and branching of the AMMA from the ATA. The AMMA should be examined carefully during ankle arthroscopy. Levels of Evidence: Level IV: Cadaveric study


2021 ◽  
Author(s):  
Song Xiao ◽  
Xiaoyu Chen ◽  
Yanna Liu

Sign in / Sign up

Export Citation Format

Share Document