scholarly journals The Macroevolutionary Consequences of Niche Construction in Microbial Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Djordje Bajić ◽  
María Rebolleda-Gómez ◽  
Martha M. Muñoz ◽  
Álvaro Sánchez
Keyword(s):  
Large Scale ◽  
Metabolic Networks ◽  
Niche Construction ◽  
De Novo ◽  
Microbial Metabolism ◽  
Microbial World ◽  
Selective Pressures ◽  
Short Piece ◽  
Patterns And Processes

Microorganisms display a stunning metabolic diversity. Understanding the origin of this diversity requires understanding how macroevolutionary processes such as innovation and diversification play out in the microbial world. Metabolic networks, which govern microbial resource use, can evolve through different mechanisms, e.g., horizontal gene transfer or de novo evolution of enzymes and pathways. This process is governed by a combination of environmental factors, selective pressures, and the constraints imposed by the genetic architecture of metabolic networks. In addition, many independent results hint that the process of niche construction, by which organisms actively modify their own and each other’s niches and selective pressures, could play a major role in microbial innovation and diversification. Yet, the general principles by which niche construction shapes microbial macroevolutionary patterns remain largely unexplored. Here, we discuss several new hypotheses and directions, and suggest metabolic modeling methods that could allow us to explore large-scale empirical genotype-phenotype-(G-P)-environment spaces in order to study the macroevolutionary effects of niche construction. We hope that this short piece will further stimulate a systematic and quantitative characterization of macroevolutionary patterns and processes in microbial metabolism.

scholarly journals The macroevolutionary consequences of niche construction in microbial metabolism

2021 ◽  
Author(s):  
Djordje Bajic ◽  
Maria Rebolleda-Gomez ◽  
Martha Munoz ◽  
Alvaro Sanchez
Keyword(s):  
Large Scale ◽  
Metabolic Networks ◽  
Niche Construction ◽  
De Novo ◽  
Microbial Metabolism ◽  
Microbial World ◽  
Selective Pressures ◽  
Short Piece ◽  
Patterns And Processes

Microorganisms display a stunning metabolic diversity. Understanding the origin of this diversity requires understanding how macroevolutionary processes such as innovation and diversification play out in the microbial world. Metabolic networks, which govern microbial resource use, can evolve through different mechanisms, e.g. horizontal gene transfer or de novo evolution of enzymes and pathways. This process is governed by a combination of environmental factors, determining selective pressures, and the constraints imposed by the complex genetic architecture of metabolic networks. In addition, many independent results hint that the process of niche construction, by which organisms actively modify their own and each other’s niches and selective pressures, could play a major role in microbial innovation and diversification. Yet, the general principles by which niche construction shapes microbial macroevolutionary patterns remain largely unexplored. Here, we discuss several new hypotheses and directions, and suggest metabolic modeling methods that could allow us to explore large-scale empirical genotype-phenotype-environment spaces in order to study the macroevolutionary effects of niche construction. We hope that this short piece will further stimulate a systematic and quantitative characterization of macroevolutionary patterns and processes in microbial metabolism.

scholarly journals Anaerobic biosynthesis of the lower ligand of vitamin B12

2015 ◽  
Vol 112 (34) ◽  
pp. 10792-10797 ◽  
Author(s):  
Amrita B. Hazra ◽  
Andrew W. Han ◽  
Angad P. Mehta ◽  
Kenny C. Mok ◽  
Vadim Osadchiy ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
De Novo ◽  
Microbial Metabolism ◽  
Obligate Anaerobic ◽  
Eubacterium Limosum ◽  
Lower Ligand ◽  
Identification And Characterization ◽  
Aerobic And Anaerobic ◽  
Unknown Component

Vitamin B12 (cobalamin) is required by humans and other organisms for diverse metabolic processes, although only a subset of prokaryotes is capable of synthesizing B12 and other cobamide cofactors. The complete aerobic and anaerobic pathways for the de novo biosynthesis of B12 are known, with the exception of the steps leading to the anaerobic biosynthesis of the lower ligand, 5,6-dimethylbenzimidazole (DMB). Here, we report the identification and characterization of the complete pathway for anaerobic DMB biosynthesis. This pathway, identified in the obligate anaerobic bacterium Eubacterium limosum, is composed of five previously uncharacterized genes, bzaABCDE, that together direct DMB production when expressed in anaerobically cultured Escherichia coli. Expression of different combinations of the bza genes revealed that 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole, all of which are lower ligands of cobamides produced by other organisms, are intermediates in the pathway. The bza gene content of several bacterial and archaeal genomes is consistent with experimentally determined structures of the benzimidazoles produced by these organisms, indicating that these genes can be used to predict cobamide structure. The identification of the bza genes thus represents the last remaining unknown component of the biosynthetic pathway for not only B12 itself, but also for three other cobamide lower ligands whose biosynthesis was previously unknown. Given the importance of cobamides in environmental, industrial, and human-associated microbial metabolism, the ability to predict cobamide structure may lead to an improved ability to understand and manipulate microbial metabolism.

scholarly journals Complementation of Cobalamin Auxotrophy in Synechococcus sp. Strain PCC 7002 and Validation of a Putative Cobalamin RiboswitchIn Vivo

2016 ◽  
Vol 198 (19) ◽  
pp. 2743-2752 ◽  
Author(s):  
Adam A. Pérez ◽  
Zhenfeng Liu ◽  
Dmitry A. Rodionov ◽  
Zhongkui Li ◽  
Donald A. Bryant
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Expression System ◽  
Industrial Applications ◽  
Methionine Synthase ◽  
Methionine Biosynthesis ◽  
Content Type ◽  
Methyl Donor ◽  
Synechococcus Sp

ABSTRACTThe euryhaline cyanobacteriumSynechococcussp. strain PCC 7002 has an obligate requirement for exogenous vitamin B12(cobalamin), but little is known about the roles of this compound in cyanobacteria. Bioinformatic analyses suggest that only the terminal enzyme in methionine biosynthesis, methionine synthase, requires cobalamin as a coenzyme inSynechococcussp. strain PCC 7002. Methionine synthase (MetH) catalyzes the transfer of a methyl group fromN5-methyl-5,6,7,8-tetrahydrofolate tol-homocysteine duringl-methionine synthesis and uses methylcobalamin as an intermediate methyl donor. Numerous bacteria and plants alternatively employ a cobalamin-independent methionine synthase isozyme, MetE, that catalyzes the same methyl transfer reaction as MetH but usesN5-methyl-5,6,7,8-tetrahydrofolate directly as the methyl donor. The cobalamin auxotrophy ofSynechococcussp. strain PCC 7002 was complemented by using themetEgene from the closely related cyanobacteriumSynechococcussp. strain PCC 73109, which possesses genes for both methionine synthases. This result suggests that methionine biosynthesis is probably the sole use of cobalamin inSynechococcussp. strain PCC 7002. Furthermore, a cobalamin-repressible gene expression system was developed inSynechococcussp. strain PCC 7002 that was used to validate the presence of a cobalamin riboswitch in the promoter region ofmetEfromSynechococcussp. strain PCC 73109. This riboswitch acts as a cobalamin-dependent transcriptional attenuator formetEin that organism.IMPORTANCESynechococcussp. strain PCC 7002 is a cobalamin auxotroph because, like eukaryotic marine algae, it uses a cobalamin-dependent methionine synthase (MetH) for the final step ofl-methionine biosynthesis but cannot synthesize cobalaminde novo. Heterologous expression ofmetE, encoding cobalamin-independent methionine synthase, fromSynechococcussp. strain PCC 73109, relieved this auxotrophy and enabled the construction of a truly autotrophicSynechococcussp. strain PCC 7002 more suitable for large-scale industrial applications. Characterization of a cobalamin riboswitch expands the genetic toolbox forSynechococcussp. strain PCC 7002 by providing a cobalamin-repressible expression system.

scholarly journals Modular, synthetic chromosomes as new tools for large scale engineering of metabolism

2021 ◽  
Author(s):  
Eline Postma ◽  
Else-Jasmijn Hassing ◽  
Venda Mangkusaputra ◽  
Jordi Geelhoed ◽  
Pilar de la Torre ◽  
...  
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Metabolic Networks ◽  
De Novo ◽  
Microbial Cell ◽  
Cell Factory ◽  
Microbial Cell Factory ◽  
Microbial Cell Factories ◽  
Cell Factories

The construction of powerful cell factories requires intensive genetic engineering for the addition of new functionalities and the remodeling of native pathways and processes. The present study demonstrates the feasibility of extensive genome reprogramming using modular, specialized de novo-assembled neochromosomes in yeast. The in vivo assembly of linear and circular neochromosomes, carrying 20 native and 21 heterologous genes, enabled the first de novo production in a microbial cell factory of anthocyanins, plant compounds with a broad range pharmacological properties. Turned into exclusive expression platforms for heterologous and essential metabolic routes, the neochromosomes mimic native chromosomes regarding mitotic and genetic stability, copy number, harmlessness for the host and editability by CRISPR/Cas9. This study paves the way for future microbial cell factories with modular genomes in which core metabolic networks, localized on satellite, specialized neochromosomes can be swapped for alternative configurations and serve as landing pads for the addition of functionalities.

scholarly journals Reconstruction of ancient microbial genomes from the human gut

Nature ◽  
2021 ◽  
Author(s):  
Marsha C. Wibowo ◽  
Zhen Yang ◽  
Maxime Borry ◽  
Alexander Hübner ◽  
Kun D. Huang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Large Scale ◽  
De Novo ◽  
Human Gut ◽  
Microbial Genomes ◽  
Functional Profiling ◽  
History Of ◽  
Southwestern Usa ◽  
Gut Microorganisms

AbstractLoss of gut microbial diversity1–6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000–2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.

scholarly journals Metage2Metabo, microbiota-scale metabolic complementarity for the identication of key species

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Arnaud Belcour ◽  
Clémence Frioux ◽  
Méziane Aite ◽  
Anthony Bretaudeau ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Functional Diversity ◽  
Large Scale ◽  
Metabolic Networks ◽  
De Novo ◽  
Functional Screening ◽  
Metabolic Cooperation ◽  
Metabolic Functions ◽  
Key Species ◽  
Genome Scale ◽  
Equivalent Properties

To capture the functional diversity of microbiota, one must identify metabolic functions and species of interest within hundreds or thousands of microorganisms. We present Metage2Metabo (M2M) a resource that meets the need for de-novo functional screening of genome-scale metabolic networks (GSMNs) at the scale of a metagenome, and the identification of critical species with respect to metabolic cooperation. M2M comprises a flexible pipeline for the characterisation of individual metabolisms and collective metabolic complementarity. In addition, M2M identifies key species, that are meaningful members of the community for functions of interest. We demonstrate that M2M is applicable to collections of genomes as well as metagenome-assembled genomes, permits an efficient GSMN reconstruction with Pathway Tools, and assesses the cooperation potential between species. M2M identifies key organisms by reducing the complexity of a large-scale microbiota into minimal communities with equivalent properties, suitable for further analyses.

Some applications of electron beam microanalysis techniques in VLSI process evaluation

1983 ◽  
Vol 41 ◽  
pp. 160-161
Author(s):  
Simon Thomas
Keyword(s):  
Integrated Circuits ◽  
Process Evaluation ◽  
Large Scale ◽  
Technology Development ◽  
Analytical Techniques ◽  
Successful Implementation ◽  
Analysis Of Failures ◽  
Characterization Of Materials ◽  
Circuits Vlsi

Trends in the technology development of very large scale integrated circuits (VLSI) have been in the direction of higher density of components with smaller dimensions. The scaling down of device dimensions has been not only laterally but also in depth. Such efforts in miniaturization bring with them new developments in materials and processing. Successful implementation of these efforts is, to a large extent, dependent on the proper understanding of the material properties, process technologies and reliability issues, through adequate analytical studies. The analytical instrumentation technology has, fortunately, kept pace with the basic requirements of devices with lateral dimensions in the micron/ submicron range and depths of the order of nonometers. Often, newer analytical techniques have emerged or the more conventional techniques have been adapted to meet the more stringent requirements. As such, a variety of analytical techniques are available today to aid an analyst in the efforts of VLSI process evaluation. Generally such analytical efforts are divided into the characterization of materials, evaluation of processing steps and the analysis of failures.

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

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