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      • Record: found
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      Recent Advances in the Discovery and Development of Marine Microbial Natural Products

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          Abstract

          Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed.

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          Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

          S D Bentley, K F Chater, A.-M. Cerdeño-Tárraga … (2002)
          Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.
          Article 0 comments Cited 741 times – based on 0 reviews     Review now
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            Production of the antimalarial drug precursor artemisinic acid in engineered yeast.

            Dae-Kyun Ro, Eric M Paradise, Mario Ouellet … (2006)
            Malaria is a global health problem that threatens 300-500 million people and kills more than one million people annually. Disease control is hampered by the occurrence of multi-drug-resistant strains of the malaria parasite Plasmodium falciparum. Synthetic antimalarial drugs and malarial vaccines are currently being developed, but their efficacy against malaria awaits rigorous clinical testing. Artemisinin, a sesquiterpene lactone endoperoxide extracted from Artemisia annua L (family Asteraceae; commonly known as sweet wormwood), is highly effective against multi-drug-resistant Plasmodium spp., but is in short supply and unaffordable to most malaria sufferers. Although total synthesis of artemisinin is difficult and costly, the semi-synthesis of artemisinin or any derivative from microbially sourced artemisinic acid, its immediate precursor, could be a cost-effective, environmentally friendly, high-quality and reliable source of artemisinin. Here we report the engineering of Saccharomyces cerevisiae to produce high titres (up to 100 mg l(-1)) of artemisinic acid using an engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450 monooxygenase (CYP71AV1) from A. annua that performs a three-step oxidation of amorpha-4,11-diene to artemisinic acid. The synthesized artemisinic acid is transported out and retained on the outside of the engineered yeast, meaning that a simple and inexpensive purification process can be used to obtain the desired product. Although the engineered yeast is already capable of producing artemisinic acid at a significantly higher specific productivity than A. annua, yield optimization and industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices.
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              Programming cells by multiplex genome engineering and accelerated evolution.

              Harris Wang, Farren J. Isaacs, Peter A Carr … (2009)
              The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales. Although in vitro and directed evolution methods have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-D-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mar Drugs
                Journal ID (iso-abbrev): Mar Drugs
                Journal ID (publisher-id): marinedrugs
                Title: Marine Drugs
                Publisher: MDPI
                ISSN (Electronic): 1660-3397
                Publication date (Electronic): 08 March 2013
                Publication date Collection: March 2013
                Volume: 11
                Issue: 3
                Pages: 700-717
                Affiliations
                [1 ]Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; E-Mails: zhqxiong@ 123456sibs.ac.cn (Z.-Q.X.); wjfecust@ 123456yahoo.com.cn (J.-F.W.); yyhao@ 123456sibs.ac.cn (Y.-Y.H.)
                [2 ]State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: yongwang@ 123456sibs.ac.cn ; Tel./Fax: +86-21-54924295.
                Article
                Publisher ID: marinedrugs-11-00700
                DOI: 10.3390/md11030700
                PMC ID: 3705366
                PubMed ID: 23528949
                SO-VID: 07ceedd5-a60b-46af-9f62-3fc75f3a0a8e
                Copyright © © 2013 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 28 December 2012
                Date revision received : 25 January 2013
                Date accepted : 06 February 2013
                Categories
                Subject: Review

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: marine microbial natural products,metagenomics,screening,genome sequencing,combinatorial biosynthesis,heterologous biosynthesis
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: marine microbial natural products, metagenomics, screening, genome sequencing, combinatorial biosynthesis, heterologous biosynthesis

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