Induction of microbial secondary metabolism.

Precursors often stimulate production of secondary metabolites either by increasing the amount of a limiting precursor, by inducing a biosynthetic enzyme (synthase) or both. These are usually amino acids but other small molecules also function as inducers. The most well-known are the auto-inducers which include gamma-butyrolactones (butanolides) of the actinomycetes, N-acylhomoserine lactones of Gram-negative bacteria, oligopeptides of Gram-positive bacteria, and B-factor (3'-[1-butylphosphoryl] adenosine) of Amycolatopsis mediterranei. The actinomycete butanolides exert their effects via receptor proteins which normally repress chemical and morphological differentiation (secondary metabolism and differentiation into aerial mycelia and spores respectively) but, when complexed with the butanolide, can no longer function. Homoserine lactones of Gram-negative bacteria function at high cell density and are structurally related to the butanolides. They turn on plant and animal virulence, light emission, plasmid transfer, and production of pigments, cyanide and beta-lactam antibiotics. They are made by enzymes homologous to Lux1, excreted by the cell, enter other cells at high density, bind to a LuxR homologue, the complex then binding to DNA upstream of genes controlled by "quorum sensing" and turning on their expression. Quorum sensing also operates in the case of the peptide pheromones of the Gram-positive bacteria. Here, secretion is accomplished by an ATP binding casette (ABC transporter), the secreted pheromone being recognized by a sensor component of a two-component signal transduction system. The pheromone often induces its own synthesis as well as those proteins involved in protein/peptide antibiotic (including bacteriocins and lantibiotics) production, virulence and genetic competence. The B-factor of A. mediterranei is an inducer of ansamycin (rifamycin) formation.     

Evolutionary basis and ecological role of toxic microbial secondary metabolites

This presentation develops a theory of the evolutionary origin and ecological implications of toxic microbial secondary metabolites. The theory is based on a model system that outlines cause—effect associations between pertinent biotypes in the aflatoxin contamination of developing maize kernels. The model suggests that the aflatoxin-producing fungi are natural digestive tract inhabitants of a number of insect species that feed on developing kernels. During feeding, the insect larvae introduce fungal propagules and provide infection sites on damaged kernels. The fungal association with insects exhibits extraordinary variability, ranging from symbiotic to pathogenic. Elaboration of aflatoxin by the fungus facilitates the pathogenic process in host insects. The theory contends that genetic information for secondary microbial metabolites evolved during ecosystem disequilibria. During periods of ecological stability, mechanisms evolved for repression of toxic secondary metabolite biosynthesis. The theory broadly suggests that contemporary agricultural activities presents the requisite milieu for production or toxic microbial secondary metabolites.     

An ecological perspective on environmental decision-making

Current research on environmental decision-makers at the professional and nonprofessional levels is reviewed. The potential utility of this research for achieving more adaptive man-environment relations in modern industrial societies is examined. A broader framework of research is suggested for viewing the antecedents and consequences of environmental decision-making from an ecological perspective. Mechanisms for promoting research on man-environment relations are considered. In particular, issues in the training of scientific man-power in this interdisciplinary field are discussed.This article was prepared while the author served as Senior Postdoctoral Fellow in Environmental Psychology at Clark University, Worcester, Massachusetts, 1970–1971.     

An ecological perspective on bacterial biodiversity

Bacteria may be one of the most abundant and species-rich groups of organisms, and they mediate many critical ecosystem processes. Despite the ecological importance of bacteria, past practical and theoretical constraints have limited our ability to document patterns of bacterial diversity and to understand the processes that determine these patterns. However, recent advances in molecular techniques that allow more thorough detection of bacteria in nature have made it possible to examine such patterns and processes. Here, we review recent studies of the distribution of free-living bacterial diversity and compare our current understanding with what is known about patterns in plant and animal diversity. From these recent studies a preliminary picture is emerging: bacterial diversity may exhibit regular patterns, and in some cases these patterns may be qualitatively similar to those observed for plants and animals.     

An environmental perspective on metabolism

In principle the knowledge of an organism's metabolic network allows to infer its biosynthetic capabilities. Handorf et al. [2005. Expanding metabolic networks: scopes of compounds, robustness, and evolution. J. Mol. Evol. 61, 498-512] developed a method of network expansion generating the set of all possible metabolites that can be produced from a set of compounds, given the structure of a metabolic network. Here we investigate the inverse problem: which chemical compounds or sets of compounds must be provided as external resources in order to sustain the growth or maintenance of an organism, given the structure of its metabolic network? Although this problem is highly combinatorial, we show that it is possible to calculate locally minimal nutrient sets that can be interpreted in terms of resource types. Using these types we predict broad nutritional requirements for 447 organisms, providing clues for possible environments from the knowledge of their metabolic networks.     

Invasive marine algae: An ecological perspective

The significance of marine algal invasion is undisputed in the global context; however, this topic has not received as much attention as it deserves. Although substantial evidence supports the fact of marine algal introduction and invasion, the underlying ecological principles need more attention to better explain such invasions. Marine algal invasions transcend national boundaries, so the problem must be considered an international problem. Commercial exploitation of invasive marine algae (and under this category we include deliberate introductions) should be undertaken, if at all, with great care and with a full understanding of all aspects of the biology and ecological consequences of the new exotic species. The aim of this article is to define algal invaders from a marine ecosystem standpoint and to discuss the different vectors, their dispersal patterns, and mechanisms of their dominance in their naturalized or introduced range     

Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective

Secondary metabolites, at least the major ones present in a plant, apparently function as defence (against herbivores, microbes, viruses or competing plants) and signal compounds (to attract pollinating or seed dispersing animals). They are thus important for the plant's survival and reproductive fitness. Secondary metabolites therefore represent adaptive characters that have been subjected to natural selection during evolution. Molecular phylogenies of the Fabaceae, Solanaceae and Lamiaceae were reconstructed and employed as a framework to map and to interpret the distribution of some major defence compounds that are typical for the respective plant families; quinolizidine alkaloids and non-protein amino acids for legumes; tropane and steroidal alkaloids for Solanaceae, and iridoids and essential oils for labiates. The distribution of the respective compounds appears to be almost mutually exclusive in the families studied, implying a strong phylogenetic and ecological component. However, on a closer look, remarkable exceptions can be observed, in that certain metabolites are absent (or present) in a given taxon, although all the neighbouring and ancestral taxa express (or do not express, respectively) the particular trait. It is argued that these patterns might reflect differential expression of the corresponding genes that have evolved earlier in plant evolution. The inconsistent secondary metabolite profiles mean that the systematic value of chemical characters becomes a matter of interpretation in the same way as traditional morphological markers. Thus, the distribution of secondary metabolites has some value for taxonomy but their occurrence apparently reflects adaptations and particular life strategies embedded in a given phylogenetic framework.     

An ecological perspective on methane emissions from northern wetlands

Wetlands are significant sources of atmospheric methane, an important radiatively active ‘greenhouse’ gas that accounts for an estimated 12% of total greenhouse warming. Since global climate models predict the greatest temperature and precipitation changes at high latitudes, and as the largest areas of wetland (346 × 10⁶ha) are in the boreal and subarctic regions (40–70°N), recent research has focused on Identifying the factors that control methane emission from northern wetlands. Over the past few years, the database has expanded tremendously, and much progress has been made in understanding the environmental controls on methane emission at small spatial and temporal scales. However, we now need to broaden our understanding of regional differences in methane emission, ecological responses of northern wetlands to climate change, and the effect of other perturbations such as drainage and flooding.     

Modeling the microbial loop: An estuarine modeler's perspective

Contemporary models of the microbial loop should be critically evaluated relative to their compartmental structures, flow networks, and treatment of upper ocean physics (vertical and horizontal boundary conditions). The development of new models that include better representation of the autotrophic components and mixotrophy/competitive interactions is warranted. The mathematical structures should reflect contemporary knowledge of controls (e.g., multiple resource limitation), thresholds and limits, and be based on testable assumptions. Stochastic processes must at some point be included to evaluate known patterns of spatial and temporal variability.     

!Kung spatial organization: An ecological and historical perspective

The ecological and social bases of spatial organization among hunters and gatherers are examined. After criticizing the patrilocal band model of social organization, the author documents the flexible, nonterritorial groupings of the !Kung Bushmen of Botswana and relates them to rainfall and surface water scarcity and variability. The paper goes on to consider the effects of extra-Bushman contacts on the breakdown of sociospatial organization and finds that the observed flexibility occurred in both the pre- and the postcontact periods. The final section attempts to relate the analysis to general issues. Three areas that need further work if a more valid model of hunter spatial organization is to be developed are the problems of time perspective in research, adaptation to long-term climatic variability, and critical thresholds of population density.     

Quantitation of microbial metabolism

Quantitation is a characteristic property of natural sciences and technologies and is the background for all kinetic and dynamic studies of microbial life. This presentation concentrates therefore on materials and methods as tools necessary to accomplish a sound, quantitative and mechanistic understanding of metabolism. Mathematical models are the software, bioreactors, actuators and analytical equipment are the hardware used. Experiments must be designed and performed in accordance with the relaxation times of the biosystem investigated; some of the respective consequences are discussed and commented in detail. Special emphasis is given to the required density, accuracy and reproducibility of data as well as their validation.     

Efficient amplification of genes involved in microbial secondary metabolism by an improved genome walking method

Genome walking is a commonly used technique for the identification of DNA sequences adjacent to known regions. Despite the development of various genome walking methods, nonspecific products are often produced in certain circumstances, especially when GC-rich DNA sequences are dealt with. To effectively resolve such technical issues, a simple nested polymerase chain reaction-based genome walking method has been developed by implementing a progressively decreased annealing temperature from 70°C to 47.5°C in the first round of amplification and a high annealing temperature of 65°C in the second round of amplification. During the entire process, a lower ramp rate of 1.5°C s⁻¹ and cooling rate of 2.5°C s⁻¹ are performed to reach the annealing temperature. Using this method, we successfully obtained the upstream and downstream sequences of three GC-rich genes involved in the biosynthetic pathways of secondary metabolites from two bacterial genomes. The efficient amplification of DNA target longer than 1.5 Kb with GC content up to 75.0% indicates that the present technique could be a valuable tool for the investigation of biosynthetic pathways of various secondary metabolites.     

Antifungal activity of microbial secondary metabolites

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi.     

Ecosystems biology of microbial metabolism

The metabolic capabilities of many environmentally and medically important microbes can be quantitatively explored using systems biology approaches to metabolic networks. Yet, as we learn more about the complex microbe-microbe and microbe-environment interactions in microbial communities, it is important to understand whether and how system-level approaches can be extended to the ecosystem level. Here we summarize recent work that addresses these challenges at multiple scales, starting from two-species natural and synthetic ecology models, up to biosphere-level approaches. Among the many fascinating open challenges in this field is whether the integration of high throughput sequencing methods and mathematical models will help us capture emerging principles of ecosystem-level metabolic organization and evolution.