**5. Uses of marine natural products**

Marine biogenic molecules are used in a large variety of applications, industrial, medical, pharmaceutical, cosmetological, as food or associated to food, decoration…

#### **5.1. Housing and transportation matters**

These include the use of fossilized or detritic materials for construction and as chemical energy sources.

#### *5.1.1. Construction materials*

resist whole-organism or whole-colony predation, or restrict their access.

polyphenols that are distasteful to fish [32].

82 Biodiversity - The Dynamic Balance of the Planet

hensive texts on the subject.

similar reasons.

actinobacteria that live in marine sediments.

Algae are generally non-toxic, but may contain antifeedants such as organohalogens or

Not all sessile, slow-moving and sedentary organisms enjoy an efficient physical protection. Fleshy invertebrate species and those that must be exposed to sunlight to perform photosyn‐ thesis may produce toxic or distasteful substances to discourage feeding by fish, crustaceans or other carnivores. Alcyonarian octocorals shelter photosymbiotic dinoflagellates, and are able to produce complex bouquets of cyclic terpenoids that are dissuasive against predators and efficient against space competitors. Sponges shelter biodiverse archaean, eubacterial and cyanobacterial communities and produce an amazing variety of metabolites (many are nitrogen containing and halogenated) as a functional consortium. Bryozoans shelter bacteria that produce highly complex and toxic molecules (e.g. bryostatins). Ascidians can produce highly bioactive molecules, such as the depsipeptidic didemnins, in association with pro‐ chloron, i.e. cyanobacteria which they cultivate in their tissues. The purpose here is not to list the thousands of amazing molecules that are produced by benthic marine invertebrates, to which we must add the recently discovered highly diverse repertoire of planktonic organisms: [31] and its updated version [33] in press) and [34] are probably the most recent and compre‐

Evolutionary reflections of chemical defenses in marine symbiotic systems have been recently proposed by [35]. Symbiotic and photosymbiotic systems that associate an invertebrate or algal host and its specific microbial consortium are common in tropical shallow water reefs, which concentrate at least one third of the total marine biodiversity and certainly the largest propor‐ tion of all known "secondary" metabolites [26]. To these must be added marine fungi and

A generally overlooked component of marine chemodiversity is mucus, sometimes constantly and abundantly produced by epithelial goblet cells of cnidarians, and also found in other sessile invertebrates, and also in fish. No two muci are alike. In fish, it helps protecting scales from unwanted fouling by encrusters or parasites, as well as having intrinsic antibacterial and antiviral properties. Coral mucus has species-specific composition and plays a role equivalent to the organ-forming mesoderm of triploblastic organisms, in managing a highly biodiverse microbial fauna that recycles carbon, nitrogen and sulfur and provides an energy complement to symbiotic photosynthesis. To the coral associated bacteria mucus plays the role of a biofilm

in which complex antibiotic interactions are at play to maintain microbial diversity.

Behavioral adaptations like "advertising" (aposematic) colors and body shapes make use of colored metabolites borrowed from the prey organisms and concentrated into superficial diverticula. Specialist predators like shell-less mollusks like dorid nudibranchs are beautifully colored and highly toxic. Several aeolid nudibranchs on the other hand use camouflage for Biogenic sand and rocks (e.g. sandstone) are used to create building, roads and associated structures. Urban architecture is mostly made of concrete structures, i.e. cemented biogenic or mineral sand and crushed rocks or debris.

#### *5.1.2. Fossil fuels and biofuels*

Fossil fuels are consumed at the rate of 88 million barrels a day, in heat engines, to produce electricity, domestic heating, and in petrochemical chemistry (plastics, clothing, lubricants, polymers). Fossil fuels are non-renewable energy, since the production rate is about onemillion times slower the consumption rate.

#### **5.2. Health and well-being**

This includes the use of biomineral or bioorganic materials in surgery, of cosmetics and skin care substances, and most of all of anticancer, antiviral, anti-pain, antibiotic, anti-inflamma‐ tory, as well as insecticidal, anti-malarial or anthelminthic molecules, not to mention other domains of growing interest, such as Alzheimer's disease and schizophrenia.

The exploitation of marine natural products in folk medicine is very limited and concerns a few organisms that did not necessitate special underwater investigations, nor entail storage and conservation problems - of paramount importance since desiccation, oxidation and fermentation occur so rapidly. Exceptions are the occasional use of specific algae as insecticides and for ringworm treatment, or the ceremonial use of toxic or venomous organisms. Fixed and fleshy organisms were generally distasteful or toxic, sparing them for being considered as remedies. Corals, sponges and a few others have no nutritional value and represent the largest biomass of high-diversity systems in tropical zones.

It is only since just after WW2 that marine organisms emerged as a complementary source to traditional plant remedies, thanks to the co-occurrence of several factors, among which (i) the recent discovery of fungal antibiotics and the use of bacterial enzymes in bioprocesses, (ii) the development of adequate screening procedures, (iii) SCUBA exploration and later robotsampling in oceanic depths. The development of synthetic chemistry soon became necessary to provide alternative sources for rare organisms, but also to find better analogues (more active, less toxic, more soluble, better tolerated, easier and cheaper to synthesize…).

A new biotechnological turn has recently been taken with the high capacity screening of vast libraries of synthetic analogues, with the development of biomimetic chemistry and with the use of genetic tools that allow bacterial carriers like *Escherichia coli* to produce a compound of interest after insertion of the set of genes sampled from the original biological source.

**5.3. High-tech**

biomedical applications [38].

and laboratory applications [42].

sewage treatment plants.

organic, fossil or live.

**6.1. Urban development**

Siliceous skeletons are transformed from dissolved silicic acid into very elaborate structures by diatoms and radiolarians. They not only serve a structural function: they allow sunlight to penetrate for photosynthesis, and there is evidence that harmful radiations are filtered out somewhat like our sunglasses, using embedded mycosporine-like amino acids as DNAprotective sunscreens [37]. Enzymes that are capable of creating optical-grade glass at room temperature are under investigation. Siliceous sponges produce glass spicules which are endowed with mechanical and optical properties unknown to manufacturers, and novel enzymatic approaches using sponge silicateins are investigated for nanotechnological and

Marine Biodiversity and Chemodiversity — The Treasure Troves of the Future

http://dx.doi.org/10.5772/57394

85

Shells of bivalve and gastropod mollusks, other than their interest as decorative items, often present amazing properties. Oyster nacre has osteo-inductive properties that could be used in bone tissue regeneration [39]. Abalone shells offer strong mechanical resistance to impact, thanks to its dual organic-limestone microscopically layered structure, inspiring novel bulletproof materials. Skeletons that are produced by sessile marine invertebrates are a great source of inspiration: some have tremendous flexibility and resilience to currents, like the horny skeleton of some gorgonians [40]; coral skeletons are used as temporary bone implants [41], coralline algae cements have amazing particle-aggregating properties, etc. Novel adhesives with high tensile strength are inspired from byssus filaments of mussels. Crab shells can provide a sustainable source of chitin and chitosan, which are used in a variety of medical

Bacteria can be modified genetically to produce pure toxins, antibiotics, polymers and enzymes with high added value. Cultivatable bacterial strains offer exciting possibilities for the transformation or the recycling of a wide range of industrial materials and agricultural waste products. Experimental biofilms can produce weak currents with potential applications in

Global anthropic influence is articulated on the exploitation of natural resources and the generation of wastes. Here are a few examples of man's use of biogenic resources, mineral and

The use of biogenic sand and limestone concretions usually involves no direct utilization of live organisms. Indirectly, the overexploitation of sand beds from littoral zones represents a double problem: the eradication of the epibenthic wildlife and with time, erosive changes in coastal profiling. Sand particles offer extended surfaces that are essential for microorganisms to recycle decaying organic debris and avoid the accumulation of toxic nitrites and nitrates. The exploitation of sands from coral reef atolls, together with the silting of coastal bays and

leeward zones due to mining activities spillage are major sources of biodiversity loss.

**6. Management of biodiversity and chemodiversity**

Marine molecular sciences have now come of age, but the exploration of novel natural products and of new biological activities must go on, especially in relation to marine microbes and to planktonic organisms.

Many (98 to 99%) of the known marine bacteria and archaea still cannot be cultivated using the existing apparatus and growth media. Knowing that invertebrates such as sponges, ascidians, bryozoans act as biological incubators of specific bacterial strains, isolated in specialized cells called bacteriocytes or allowed to interact synergistically, there is a world of possibilities opened for us to investigate. After all, we only discovered recently that bacteria have a form of social life within biofilms, have developed a chemical language that allows their populations to be regulated, have an instrumental role in carbon and nitrogen cycling in holobiont photosystems such as corals, lichens etc. and in biogeochemical cycles at large [28].

Indeed we still have no idea of the importance bacteria have in the production or in the modulation of the genetic expression of key metabolites hitherto attributed to their host organisms, except through limited attempts to cultivate the latter axenically. Using a systems biology approach, stress transcriptomics studies will undoubtedly help us achieve better control of the production of key enzymes or key defense metabolites from host organisms, as well as evaluate the optimal conditions for the maintenance of a rich and diverse microflora using metagenomics.

The purpose here is not to list the bioactive molecules that have been discovered, elucidated, synthesized, nor to detail their bioactivities. Excellent reviews are regularly updated on the subject, presented by natural products chemists and pharmacologists. Interactive databases include standard spectral information, and sophisticated algorithms are available as aids for structure elucidation and as dereplication tools. Two recent and outstanding information sources are [31] and its updated version [33], and [34].

Well over 20,000 secondary metabolites have been screened so far, but only a handful is now legally approved for use as prescription drugs or treatments by the Food and Drugs Admin‐ istration (FDA) and by the European Union since 1974 (see [36] and updates thereof in: http:// marinepharmacology.midwestern.edu/clinPipeline.htm). Successful molecules and ana‐ logues have to undergo in-vitro, in-vivo (preclinical) tests and finally several rounds of clinical trials on patients, a process known as the clinical pipeline. On average, each development costs about one billion dollars over a period of ten years, and there is great pressure to discover and develop novel molecules, especially against various types of cancer, antibiotics against resistant strains, and molecules for the treatment of neurodegenerative diseases. With energy, food and housing, pharmaceuticals represent a primary resource in modern economy.

### **5.3. High-tech**

A new biotechnological turn has recently been taken with the high capacity screening of vast libraries of synthetic analogues, with the development of biomimetic chemistry and with the use of genetic tools that allow bacterial carriers like *Escherichia coli* to produce a compound of

Marine molecular sciences have now come of age, but the exploration of novel natural products and of new biological activities must go on, especially in relation to marine microbes and to

Many (98 to 99%) of the known marine bacteria and archaea still cannot be cultivated using the existing apparatus and growth media. Knowing that invertebrates such as sponges, ascidians, bryozoans act as biological incubators of specific bacterial strains, isolated in specialized cells called bacteriocytes or allowed to interact synergistically, there is a world of possibilities opened for us to investigate. After all, we only discovered recently that bacteria have a form of social life within biofilms, have developed a chemical language that allows their populations to be regulated, have an instrumental role in carbon and nitrogen cycling in holobiont photosystems such as corals, lichens etc. and in biogeochemical cycles at large [28].

Indeed we still have no idea of the importance bacteria have in the production or in the modulation of the genetic expression of key metabolites hitherto attributed to their host organisms, except through limited attempts to cultivate the latter axenically. Using a systems biology approach, stress transcriptomics studies will undoubtedly help us achieve better control of the production of key enzymes or key defense metabolites from host organisms, as well as evaluate the optimal conditions for the maintenance of a rich and diverse microflora

The purpose here is not to list the bioactive molecules that have been discovered, elucidated, synthesized, nor to detail their bioactivities. Excellent reviews are regularly updated on the subject, presented by natural products chemists and pharmacologists. Interactive databases include standard spectral information, and sophisticated algorithms are available as aids for structure elucidation and as dereplication tools. Two recent and outstanding information

Well over 20,000 secondary metabolites have been screened so far, but only a handful is now legally approved for use as prescription drugs or treatments by the Food and Drugs Admin‐ istration (FDA) and by the European Union since 1974 (see [36] and updates thereof in: http:// marinepharmacology.midwestern.edu/clinPipeline.htm). Successful molecules and ana‐ logues have to undergo in-vitro, in-vivo (preclinical) tests and finally several rounds of clinical trials on patients, a process known as the clinical pipeline. On average, each development costs about one billion dollars over a period of ten years, and there is great pressure to discover and develop novel molecules, especially against various types of cancer, antibiotics against resistant strains, and molecules for the treatment of neurodegenerative diseases. With energy, food and housing, pharmaceuticals represent a primary resource in modern economy.

interest after insertion of the set of genes sampled from the original biological source.

planktonic organisms.

84 Biodiversity - The Dynamic Balance of the Planet

using metagenomics.

sources are [31] and its updated version [33], and [34].

Siliceous skeletons are transformed from dissolved silicic acid into very elaborate structures by diatoms and radiolarians. They not only serve a structural function: they allow sunlight to penetrate for photosynthesis, and there is evidence that harmful radiations are filtered out somewhat like our sunglasses, using embedded mycosporine-like amino acids as DNAprotective sunscreens [37]. Enzymes that are capable of creating optical-grade glass at room temperature are under investigation. Siliceous sponges produce glass spicules which are endowed with mechanical and optical properties unknown to manufacturers, and novel enzymatic approaches using sponge silicateins are investigated for nanotechnological and biomedical applications [38].

Shells of bivalve and gastropod mollusks, other than their interest as decorative items, often present amazing properties. Oyster nacre has osteo-inductive properties that could be used in bone tissue regeneration [39]. Abalone shells offer strong mechanical resistance to impact, thanks to its dual organic-limestone microscopically layered structure, inspiring novel bulletproof materials. Skeletons that are produced by sessile marine invertebrates are a great source of inspiration: some have tremendous flexibility and resilience to currents, like the horny skeleton of some gorgonians [40]; coral skeletons are used as temporary bone implants [41], coralline algae cements have amazing particle-aggregating properties, etc. Novel adhesives with high tensile strength are inspired from byssus filaments of mussels. Crab shells can provide a sustainable source of chitin and chitosan, which are used in a variety of medical and laboratory applications [42].

Bacteria can be modified genetically to produce pure toxins, antibiotics, polymers and enzymes with high added value. Cultivatable bacterial strains offer exciting possibilities for the transformation or the recycling of a wide range of industrial materials and agricultural waste products. Experimental biofilms can produce weak currents with potential applications in sewage treatment plants.
