Biological composites—complex structures for functional diversity

The bulk of Earth’s biological materials consist of few base substances—essentially proteins, polysaccharides, and minerals—that assemble into large varieties of structures. Multifunctionality arises naturally from this structural complexity: An example is the combination of rigidity and flexibility in protein-based teeth of the squid sucker ring. Other examples are time-delayed actuation in plant seed pods triggered by environmental signals, such as fire and water, and surface nanostructures that combine light manipulation with mechanical protection or water repellency. Bioinspired engineering transfers some of these structural principles into technically more relevant base materials to obtain new, often unexpected combinations of material properties. Less appreciated is the huge potential of using bioinspired structural complexity to avoid unnecessary chemical diversity, enabling easier recycling and, thus, a more sustainable materials economy.

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Analysis of a large food chemical database: chemical space, diversity, and complexity

F1000Research ◽

10.12688/f1000research.15440.2 ◽

2018 ◽

Vol 7 ◽

pp. 993 ◽

Cited By ~ 14

Author(s):

J. Jesús Naveja ◽

Mariel P. Rico-Hidalgo ◽

José L. Medina-Franco

Keyword(s):

Natural Products ◽

Chemical Space ◽

Structural Complexity ◽

Chemical Diversity ◽

Chemical Structures ◽

Novel Approach ◽

Chemical Database ◽

Protein Interactome ◽

Limited Basis ◽

Future Direction

Background: Food chemicals are a cornerstone in the food industry. However, its chemical diversity has been explored on a limited basis, for instance, previous analysis of food-related databases were done up to 2,200 molecules. The goal of this work was to quantify the chemical diversity of chemical compounds stored in FooDB, a database with nearly 24,000 food chemicals. Methods: The visual representation of the chemical space of FooDB was done with ChemMaps, a novel approach based on the concept of chemical satellites. The large food chemical database was profiled based on physicochemical properties, molecular complexity and scaffold content. The global diversity of FooDB was characterized using Consensus Diversity Plots. Results: It was found that compounds in FooDB are very diverse in terms of properties and structure, with a large structural complexity. It was also found that one third of the food chemicals are acyclic molecules and ring-containing molecules are mostly monocyclic, with several scaffolds common to natural products in other databases. Conclusions: To the best of our knowledge, this is the first analysis of the chemical diversity and complexity of FooDB. This study represents a step further to the emerging field of “Food Informatics”. Future study should compare directly the chemical structures of the molecules in FooDB with other compound databases, for instance, drug-like databases and natural products collections. An additional future direction of this work is to use the list of 3,228 polyphenolic compounds identified in this work to enhance the on-going polyphenol-protein interactome studies.

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Tellurium Minerals: Structural and Chemical Diversity and Complexity

Minerals ◽

10.3390/min10070623 ◽

2020 ◽

Vol 10 (7) ◽

pp. 623

Author(s):

Vladimir G. Krivovichev ◽

Sergey V. Krivovichev ◽

Marina V. Charykova

Keyword(s):

Statistical Analysis ◽

Chemical Weathering ◽

Chemical Elements ◽

Structural Complexity ◽

Ore Deposits ◽

Chemical Diversity ◽

Mineral Species ◽

Hydrothermal Solutions ◽

Informational Entropy ◽

Reducing Conditions

The chemical diversity and complexity of tellurium minerals were analyzed using the concept of mineral systems and Shannon informational entropy. The study employed data for 176 Te mineral species known today. Tellurium minerals belong to six mineral systems in the range of one-to-six species-defining elements. For 176 tellurium minerals, only 36 chemical elements act as essential species-defining constituents. The numbers of minerals of main elements are calculated as follows (the number of mineral species is given in parentheses): O (89), H (48), Cu (48), Pb (43), Bi (31), S (29), Ag (20), Fe (20), Pd (16), Cl (13), and Zn (11). In accordance with their chemistry, all Te minerals are classified into five types of mineral systems: tellurium, oxides, tellurides and intermetalides, tellurites, and tellurates. A statistical analysis showed positive relationships between the chemical, structural, and crystallochemical complexities and the number of essential species-defining elements in a mineral. A positive statistically significant relationship between chemical and structural complexities was established. It is shown that oxygen-free and oxygen-bearing Te minerals differ sharply from each other in terms of chemical and structural complexity, with the first group of minerals being simpler than the second group. The oxygen-free Te minerals (tellurium, tellurides, and intermetallides) are formed under reducing conditions with the participation of hydrothermal solutions. The most structurally complex oxygen-bearing Te minerals originate either from chemical weathering and the oxidation of ore deposits or from volcanic exhalations (Nabokoite).

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GPAHex-A synthetic biology platform for Type IV–V glycopeptide antibiotic production and discovery

Nature Communications ◽

10.1038/s41467-020-19138-5 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Min Xu ◽

Wenliang Wang ◽

Nicholas Waglechner ◽

Elizabeth J. Culp ◽

Allison K. Guitor ◽

...

Keyword(s):

Synthetic Biology ◽

Antibiotic Production ◽

Structural Complexity ◽

Fold Increase ◽

Building Blocks ◽

Chemical Diversity ◽

Glycopeptide Antibiotics ◽

Gram Positive Bacteria ◽

Type Iv

Abstract Glycopeptide antibiotics (GPAs) are essential for the treatment of severe infectious diseases caused by Gram-positive bacteria. The emergence and spread of GPA resistance have propelled the search for more effective GPAs. Given their structural complexity, genetic intractability, and low titer, expansion of GPA chemical diversity using synthetic or medicinal chemistry remains challenging. Here we describe a synthetic biology platform, GPAHex (GPA Heterologous expression), which exploits the genes required for the specialized GPA building blocks, regulation, antibiotic transport, and resistance for the heterologous production of GPAs. Application of the GPAHex platform results in: (1) a 19-fold increase of corbomycin titer compared to the parental strain, (2) the discovery of a teicoplanin-class GPA from an Amycolatopsis isolate, and (3) the overproduction and characterization of a cryptic nonapeptide GPA. GPAHex provides a platform for GPA production and mining of uncharacterized GPAs and provides a blueprint for chassis design for other natural product classes.

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Endophytic Fungi from Terminalia Species: A Comprehensive Review

Journal of Fungi ◽

10.3390/jof5020043 ◽

2019 ◽

Vol 5 (2) ◽

pp. 43 ◽

Cited By ~ 6

Author(s):

Rufin Marie Kouipou Toghueo ◽

Fabrice Fekam Boyom

Keyword(s):

Secondary Metabolites ◽

Endophytic Fungi ◽

Biological Activities ◽

Fungal Endophytes ◽

Structural Complexity ◽

Chemical Diversity ◽

Antioxidant Compounds ◽

Comprehensive Review ◽

Biological Potential ◽

Insight Into

Endophytic fungi have proven their usefulness for drug discovery, as suggested by the structural complexity and chemical diversity of their secondary metabolites. The diversity and biological activities of endophytic fungi from the Terminalia species have been reported. Therefore, we set out to discuss the influence of seasons, locations, and even the plant species on the diversity of endophytic fungi, as well as their biological activities and secondary metabolites isolated from potent strains. Our investigation reveals that among the 200–250 Terminalia species reported, only thirteen species have been studied so far for their endophytic fungi content. Overall, more than 47 fungi genera have been reported from the Terminalia species, and metabolites produced by some of these fungi exhibited diverse biological activities including antimicrobial, antioxidant, antimalarial, anti-inflammatory, anti-hypercholesterolemic, anticancer, and biocontrol varieties. Moreover, more than 40 compounds with eighteen newly described secondary metabolites were reported; among these, metabolites are the well-known anticancer drugs, a group that includes taxol, antioxidant compounds, isopestacin, and pestacin. This summary of data illustrates the considerable diversity and biological potential of fungal endophytes of the Terminalia species and gives insight into important findings while paving the way for future investigations.

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Phytotoxin production in Aspergillus terreus is regulated by independent environmental signals

eLife ◽

10.7554/elife.07861 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 31

Author(s):

Markus Gressler ◽

Florian Meyer ◽

Daniel Heine ◽

Peter Hortschansky ◽

Christian Hertweck ◽

...

Keyword(s):

Aspergillus Terreus ◽

Response Regulator ◽

Biological Activities ◽

Biological Effects ◽

Response Regulators ◽

Iron Starvation ◽

Nitrogen Response ◽

Plant Seed ◽

Environmental Signals ◽

Physiological Relevance

Secondary metabolites have a great potential as pharmaceuticals, but there are only a few examples where regulation of gene cluster expression has been correlated with ecological and physiological relevance for the producer. Here, signals, mediators, and biological effects of terrein production were studied in the fungus Aspergillus terreus to elucidate the contribution of terrein to ecological competition. Terrein causes fruit surface lesions and inhibits plant seed germination. Additionally, terrein is moderately antifungal and reduces ferric iron, thereby supporting growth of A. terreus under iron starvation. In accordance, the lack of nitrogen or iron or elevated methionine levels induced terrein production and was dependent on either the nitrogen response regulators AreA and AtfA or the iron response regulator HapX. Independent signal transduction allows complex sensing of the environment and, combined with its broad spectrum of biological activities, terrein provides a prominent example of adapted secondary metabolite production in response to environmental competition.

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Evolution of chemical diversity by coordinated gene swaps in type II polyketide gene clusters

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1511688112 ◽

2015 ◽

Vol 112 (45) ◽

pp. 13952-13957 ◽

Cited By ~ 29

Author(s):

Maureen E. Hillenmeyer ◽

Gergana A. Vandova ◽

Erin E. Berlew ◽

Louise K. Charkoudian

Keyword(s):

Rational Design ◽

Large Scale ◽

Biological Activities ◽

Structural Complexity ◽

Gene Clusters ◽

Lessons Learned ◽

Chemical Diversity ◽

Type Ii ◽

Cellular Processes ◽

Wide Scale

Natural product biosynthetic pathways generate molecules of enormous structural complexity and exquisitely tuned biological activities. Studies of natural products have led to the discovery of many pharmaceutical agents, particularly antibiotics. Attempts to harness the catalytic prowess of biosynthetic enzyme systems, for both compound discovery and engineering, have been limited by a poor understanding of the evolution of the underlying gene clusters. We developed an approach to study the evolution of biosynthetic genes on a cluster-wide scale, integrating pairwise gene coevolution information with large-scale phylogenetic analysis. We used this method to infer the evolution of type II polyketide gene clusters, tracing the path of evolution from the single ancestor to those gene clusters surviving today. We identified 10 key gene types in these clusters, most of which were swapped in from existing cellular processes and subsequently specialized. The ancestral type II polyketide gene cluster likely comprised a core set of five genes, a roster that expanded and contracted throughout evolution. A key C24 ancestor diversified into major classes of longer and shorter chain length systems, from which a C20 ancestor gave rise to the majority of characterized type II polyketide antibiotics. Our findings reveal that (i) type II polyketide structure is predictable from its gene roster, (ii) only certain gene combinations are compatible, and (iii) gene swaps were likely a key to evolution of chemical diversity. The lessons learned about how natural selection drives polyketide chemical innovation can be applied to the rational design and guided discovery of chemicals with desired structures and properties.

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The Biological and Chemical Diversity of Tetramic Acid Compounds from Marine-Derived Microorganisms

Marine Drugs ◽

10.3390/md18020114 ◽

2020 ◽

Vol 18 (2) ◽

pp. 114

Author(s):

Minghua Jiang ◽

Senhua Chen ◽

Jing Li ◽

Lan Liu

Keyword(s):

Biological Activities ◽

Structural Complexity ◽

Cyclopiazonic Acid ◽

Chemical Diversity ◽

Tetramic Acid ◽

The Past ◽

Acid Type ◽

Tetramic Acids ◽

Research Studies

Tetramic acid (pyrrolidine-2,4-dione) compounds, isolated from a variety of marine and terrestrial organisms, have attracted considerable attention for their diverse, challenging structural complexity and promising bioactivities. In the past decade, marine-derived microorganisms have become great repositories of novel tetramic acids. Here, we discuss the biological activities of 277 tetramic acids of eight classifications (simple 3-acyl tetramic acids, 3-oligoenoyltetramic acids, 3-decalinoyltetramic acid, 3-spirotetramic acids, macrocyclic tetramic acids, N-acylated tetramic acids, α-cyclopiazonic acid-type tetramic acids, and other tetramic acids) from marine-derived microbes, including fungi, actinobacteria, bacteria, and cyanobacteria, as reported in 195 research studies up to 2019.

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Selenium Minerals: Structural and Chemical Diversity and Complexity

Minerals ◽

10.3390/min9070455 ◽

2019 ◽

Vol 9 (7) ◽

pp. 455 ◽

Cited By ~ 3

Author(s):

Vladimir G. Krivovichev ◽

Sergey V. Krivovichev ◽

Marina V. Charykova

Keyword(s):

Chemical Elements ◽

Structural Complexity ◽

Essential Element ◽

Closed Shell ◽

Unit Cell ◽

Chemical Diversity ◽

Near Surface ◽

International Mineralogical Association ◽

Chemical Complexity ◽

Essential Components

Chemical diversity of minerals containing selenium as an essential element has been analyzed in terms of the concept of mineral systems and the information-based structural and chemical complexity parameters. The study employs data for 123 Se mineral species approved by the International Mineralogical Association as of 25 May 2019. All known selenium minerals belong to seven mineral systems with the number of essential components ranging from one to seven. According to their chemical features, the minerals are subdivided into five groups: Native selenium, oxides, selenides, selenites, and selenates. Statistical analysis shows that there are strong and positive correlations between the chemical and structural complexities (measured as amounts of Shannon information per atom and per formula or unit cell) and the number of different chemical elements in a mineral. Analysis of relations between chemical and structural complexities provides strong evidence that there is an overall trend of increasing structural complexity with the increasing chemical complexity. The average structural complexity for Se minerals is equal to 2.4(1) bits per atom and 101(17) bits per unit cell. The chemical and structural complexities of O-free and O-bearing Se minerals are drastically different with the first group being simpler and the second group more complex. The O-free Se minerals (selenides and native Se) are primary minerals; their formation requires reducing conditions and is due to hydrothermal activity. The O-bearing Se minerals (oxides and oxysalts) form in near-surface environment, including oxidation zones of mineral deposits, evaporites and volcanic fumaroles. From the structural viewpoint, the five most complex Se minerals are marthozite, Cu(UO2)3(SeO3)2O2·8H2O (744.5 bits/cell); mandarinoite, Fe2(SeO3)3·6H2O (640.000 bits/cell); carlosruizite, K6Na4Na6Mg10(SeO4)12(IO3)12·12H2O (629.273 bits/cell); prewittite, KPb1.5ZnCu6O2(SeO3)2Cl10 (498.1 bits/cell); and nicksobolevite, Cu7(SeO3)2O2Cl6 (420.168 bits/cell). The mechanisms responsible for the high structural complexity of these minerals are high hydration states (marthozite and mandarinoite), high topological complexity (marthozite, mandarinoite, carlosruizite, nicksobolevite), high chemical complexity (prewittite and carlosruizite), and the presence of relatively large clusters of atoms (carlosruizite and nicksobolevite). In most cases, selenium itself does not play the crucial role in determining structural complexity (there are structural analogues or close species of marthozite, mandarinoite, and carlosruizite that do not contain Se), except for selenite chlorides, where stability of crystal structures is adjusted by the existence of attractive Se–Cl closed-shell interactions impossible for sulfates or phosphates. Most structurally complex Se minerals originate either from relatively low-temperature hydrothermal environments (as marthozite, mandarinoite, and carlosruizite) or from mild (500–700 °C) anhydrous gaseous environments of volcanic fumaroles (prewittite, nicksobolevite).

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Analysis of a large food chemical database: chemical space, diversity, and complexity

F1000Research ◽

10.12688/f1000research.15440.1 ◽

2018 ◽

Vol 7 ◽

pp. 993 ◽

Cited By ~ 4

Author(s):

J. Jesús Naveja ◽

Mariel P. Rico-Hidalgo ◽

José L. Medina-Franco

Keyword(s):

Natural Products ◽

Chemical Space ◽

Structural Complexity ◽

Chemical Compounds ◽

Chemical Diversity ◽

Chemical Structures ◽

Novel Approach ◽

Chemical Database ◽

Molecular Complexity ◽

Limited Basis

Background: Food chemicals are a cornerstone in the food industry. However, its chemical diversity has been explored on a limited basis, for instance, previous analysis of food-related databases were done up to 2,200 molecules. The goal of this work was to quantify the chemical diversity of chemical compounds stored in FooDB, a database with nearly 24,000 food chemicals. Methods: The visual representation of the chemical space of FooDB was done with ChemMaps, a novel approach based on the concept of chemical satellites. The large food chemical database was profiled based on physicochemical properties, molecular complexity and scaffold content. The global diversity of FoodDB was characterized using Consensus Diversity Plots. Results: It was found that compounds in FooDB are very diverse in terms of properties and structure, with a large structural complexity. It was also found that one third of the food chemicals are acyclic molecules and ring-containing molecules are mostly monocyclic, with several scaffolds common to natural products in other databases. Conclusions: To the best of our knowledge, this is the first analysis of the chemical diversity and complexity of FooDB. This study represents a step further to the emerging field of “Food Informatics”. Future study should compare directly the chemical structures of the molecules in FooDB with other compound databases, for instance, drug-like databases and natural products collections.

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Combined MS/MS-NMR Annotation Guided Discovery of Iris lactea var. chinensis Seed as a Source of Viral Neuraminidase Inhibitory Polyphenols

Molecules ◽

10.3390/molecules25153383 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3383

Author(s):

Hyun Woo Kim ◽

Soo Sung Kim ◽

Kyo Bin Kang ◽

Byeol Ryu ◽

Eunjin Park ◽

...

Keyword(s):

Inhibitory Concentration ◽

Health Benefit ◽

Dry Weight ◽

Chemical Diversity ◽

Nmr Analysis ◽

Chemical Profile ◽

Guided Discovery ◽

Plant Seed ◽

Ic50 Values ◽

Inhibitory Activities

In this study, the chemical diversity of polyphenols in Iris lactea var. chinensis seeds was identified by combined MS/MS-NMR analysis. Based on the annotated chemical profile, the isolation of stilbene oligomers was conducted, and consequently, stilbene oligomers (1-10) were characterized. Of these, compounds 1 and 2 are previously undescribed stilbene dimer glycoside (1) and tetramer glycoside (2), respectively. Besides, to evaluate this plant seed as a rich source of stilbene oligomers, we quantified three stilbene oligomers of I. lactea var. chinensis seeds. The contents of three major stilbene oligomers—trans-ε-viniferin (3), vitisin A (6), and vitisin B (9)—in I. lactea var. chinensis seeds were quantified as 2.32 (3), 4.95 (6), and 1.64 (9) mg/g dry weight (DW). All the isolated compounds were tested for their inhibitory activities against influenza neuraminidase. Compound 10 was found to be active with the half maximal inhibitory concentration (IC50) values at 4.76 μM. Taken together, it is concluded that I. lactea var. chinensis seed is a valuable source of stilbene oligomers with a human health benefit.

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