Frontiers in Marine Biotechnology Chapter Abstracts
Chapter 1
Implications of Marine Biotechnology on Drug Discovery
Peter Proksch, Ru Angelie Edrada, and Wen Han Lin
Abstract
The quest for drugs from the sea has yielded an impressive list of natural products mostly from invertebrates such as sponges, tunicates, bryozoans and others that are either in late stages of clinical trials whereas a few have already entered the market. More recently, marine-derived microorganisms such as bacteria, fungi, cyanobacteria and other microalgae have also come into the focus of marine drug prospection. The low yields of compounds that are produced by many marine invertebrates but also by numerous marine microorganisms have proven to be a severe obstacle for the development of promising compounds. Due to the structural complexity of most marine natural products total synthesis is not feasible in many cases. Alternative strategies aiming at a sustainable supply of marine derived drugs are needed and are discussed in this chapter. One strategy which holds promises for the future is mariculture of marine invertebrates such as bryozoans, sponges, tunicates and others. Other efforts aim at the isolation and subsequent cultivation of various microorganisms from their invertebrate hosts. Striking structural similarities that are frequently observed between natural products from marine invertebrates and compounds isolated from microorganisms give indeed support to the hypothesis that numerous bioactive compounds of invertebrate origin are in fact microbial metabolites originating from dietary, commensalic or "endosymbiotic" microorganisms. Further support for this hypothesis comes from molecular biological studies which led to the isolation and characterization of putative biosynthetic gene clusters such as polyketide synthases or nonribosomal peptide synthetases from microorganisms that are associated with marine invertebrates that are the source of "microbial-type" natural products. It is hoped that the development of efficient cloning strategies will eventually allow a heterologous production of marine drugs through means of recombinant technology. Success in the implementation of mostly biotechnological methods for a sustainable supply of bioactive natural products will be crucial for the future success of marine drug discovery.
Chapter 2
The Promise of Aquaculture for Delivering Sustainable Supplies of New Drugs From The Sea: Examples From In-Sea and Tank-Based Invertebrate Culture Projects From Around The World
Dominick Mendola, Santiago A. Naranjo Lozano, Alan R. Duckworth, and Ronald Osinga
Abstract
In the mid-1980s it was suggested that aquaculture production technology developed for food species such as fish and shrimp could be applied to produce large-scale supplies of marine invertebrates for their bioactive chemical constituents. Since then a relatively small number of pharmaceutical aquaculture projects of any appreciable scale have been implemented. These projects have cultured representatives from primarily four major phyla of sessile marine invertebrates: Bryozoa, Chordata, Coelenterata and Porifera either in the sea, or in tanks on land. In this chapter we present representative case history examples of some of the better documented projects, including a commercial scale in-sea culture project implemented in the W. Mediterranean by the pioneering Spanish marine pharmaceutical company PharmaMar, S.A.U. This project produced drug materials (250 MT total) for pre-clinical and clinical studies of the promising anticancer compound Yondelis ™ (ET-743) from cultures of the colonial ascidian Ecteinascidia turbinata, and remains as the world's first and best example of the promise of aquaculture for supplying commercial quantities of: "New Drugs from the Sea".
Chapter 3
Secondary Metabolites From Marine-derived Fungi
Rainer Ebel
Abstract
Marine-derived fungi continue to produce a plethora of novel secondary metabolites, some of them featuring new carbon framework hitherto unprecedented at least from nature, and many of them exhibiting interesting biological and pharmacological properties. This review with 240 structures and 284 references focuses on new structures identified from fungi from marine habitats in comparison to those already known from terrestrial strains, covering the period between 2002 and 2004. In addition, a brief overview of the biological aspects of marine-derived fungi relevant to natural products chemistry as well as other applications such as biotechnological use of this interesting group of organisms is given.
Chapter 4
Microalgae as a Source of Bioactive Molecules: Special Problems and Methodology
Yuzuru Shimizu and Bo Li
Abstract
Microalgae have shown a great potential to produce completely new types of bioactive compounds. In this chapter, the recent progress in the area is presented with an emphasis on the protoctista group of organisms such as dinoflagellates. The uniqueness of their biosynthetic pathways and mechanisms, which seem to be important for gene analysis and possible biotechnological production of much needed metabolites, is discussed. Also described are the actual procedures and techniques used in the isolation and culturing of microalgae for screening of anticancer and other bioactive compounds.
Chapter 5
The Secondary Metabolites and Biosynthetic Gene Clusters of Marine Cyanobacteria. Applications in Biotechnology
Aishwarya V. Ramaswamy, Patricia M. Flatt, Daniel J. Edwards, T. Luke Simmons, Bingnan Han and William H. Gerwick
Abstract
Marine cyanobacteria have proven to be one of the most versatile marine producers of secondary metabolites. Many of these metabolites demonstrate antiproliferative activity (e.g. curacin A, dolastatins), acute cytotoxic activity (e.g. apratoxin, hectochlorin) or have specific neurotoxic activity (e.g. kalkitoxin, antillatoxin), making them invaluable as potential therapeutic leads or pharmacological tools. The predominant biogenetic theme in cyanobacterial natural products chemistry is the integration of polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS) along with a variety of unusual tailoring or modifying enzymes, and accounts for the tremendous structural diversity of their metabolites. Only recently has the genetic architecture of several cyanobacterial biosynthetic gene clusters been determined, and studies to understand and exploit this biosynthentic machinery present an exciting new frontier. This chapter will summarize the properties of several notable metabolites from marine cyanobacteria that have clinical or pharmacological applications followed by a detailed account of their biosyntheses at the molecular genetic level and their potential applications in biotechnology.
Chapter 6
Marine Bacterial Metabolites
Hartmut Laatsch
Abstract
In the past few years, a remarkable number of structurally unique and highly active metabolites has been published from marine bacteria, and especially marine actinomycetes have shown an impressive metabolic capacity. If these bacterial isolates are really indigenous to the marine environment is, however, often not proven. After decades of research mainly on terrestrial microbes, the yearly output of the marine research has passed now its terrestrial counterpart. This chapter summarizes the development of the marine microbial research since the year 2000.
Chapter 7
Microorganisms of Sponges: Phylogenetic Diversity and Biotechnological Potential
Matthias Scheuermayer, Sheila Pimentel-Elardo, Lars Fieseler, Lubomir Grozdanov, Ute Hentschel
Abstract
Marine sponges (Porifera) are a rich source of secondary metabolites. More than 12,000 compounds have been isolated from marine sources, the majority of which stems from sponges. Because many species are also associated with enormous amounts of microorganisms they can be considered as 'microbial fermenters' that hold a largely untapped potential for biotechnological applications. Cultivation of bacteria and fungi from sponges continues to yield novel bioactive metabolites. The implementation of cultivation-independent techniques using the 16S rRNA gene as a phylogenetic marker has provided unprecedented insights into the microbial community composition of marine sponges. Particularly phyla that contain few or no cultivated representatives (i.e., Chloroflexi, Acidobacteria, Gemmatimonadetes, Candidate phylum 'Poribacteria') are numerically abundant and metabolically active in sponges. This book chapter provides an overview over the recent insights into the microbial diversity and biotechnological potential of sponges.
Chapter 8
How Does a Marine Sponge Suberites domuncula Cope With the Epibacterial Threat? Experimental Evidence From Molecular Biological Approach
Narsinh L. Thakur and Werner E. G. MMüller
Abstract
Marine sponges are threatened by an abundance of microorganisms from the surrounding environment; they have, however, developed several strategies to cope with this threat. Sponges produce antibacterial proteins and bioactive secondary metabolites for epibacterial defense. Molecular biological analysis showed up-regulation of antibacterial molecules producing genes in sponges in response to the bacterial stress. This could be considered as direct defense strategy. Sponges also harbor some bacteria, which can deter other microbes from the surrounding environment and thus indirectly help sponges in epibacterial defense. In the present review, the epibacterial defense strategy of the marine sponge Suberites domuncula is outlined out with special emphasis on molecular biological studies to understand its interaction with bacteria. Direct and indirect defense strategies of this sponge are supported with experimental evidence.
Chapter 9
Genomic and Metagenomic Strategies to Identify Biosynthetic Gene Clusters in Uncultivated Symbionts of Marine Invertebrates
Daniel Butzke and Jörn Piel
Abstract
One of the biggest impediments in the development of drug candidates isolated from marine animals is the creation of a long-term, sustainable supply. Only in rare cases do economic production methods as alternatives to mass harvestings exist, such as semi- or total synthesis. There is a growing body of evidence that many marine natural products are produced by microorganisms living associated with the animal hosts. These microbes are so far recalcitrant to any culturing attempts, thus making their direct study and exploitation for sustainable drug production difficult. In this review, we give a survey of recent genetic methods to investigate and harness the pharmaceutical potential of natural product symbioses. The isolation of biosynthetic genes from animal metagenomes can not only provide detailed insights into the chemistry and biology of symbiotic producers but should in principle allow to establish environmentally sound production systems by heterologous gene expression for a wide range of drug candidates. The principal current obstacle to a general application of this strategy is the complexity of many host-symbiont metagenomes, which complicates a straightforward identification of the desired genes.
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