La catalyse par les métaux de transition a pris une ampleur considérable depuis quelques décennies et est devenue un outil puissant en chimie organométallique. La réaction de CH ortho fonctionnalisation, impliquant une catalyse duale palladium/norbornène, découverte à la fin des années 90, a permis une grande avancée dans le domaine des réactions multi-composantes. Elle permet d’accéder à des structures polycycliques via un mécanisme original, impliquant la formation d’un palladacycle. Elle constitue également la première réaction catalytique incluant trois états d’oxydation du palladium (0, II et IV). Dans un contexte où la chimie tend à être plus éco-compatible, nous souhaitions tirer avantage de cette réaction pour la synthèse de dibenzoazépines. Ils représentent en effet d’intéressants motifs utilisés aussi bien en organocatalyse que comme composés bioactifs, cependant les synthèses existant à ce jour ne permettent pas de diversifier la structure de ces molécules et requièrent souvent des séquences multiples étapes ou des réactifs toxiques. La synthèse de dibenzoazépines a ainsi été réalisée selon une approche à trois composants incluant une bromobenzylamine, un iodure aromatique ortho substitué et une oléfine portant un groupement électro-attracteur via une séquence de CH ortho fonctionnalisation/Heck/aza-Michael. Remarquablement, cette dernière étape présente une diastéréosélectivité totale. L’emploi de bromobenzylamine substituée racémique montre la même sélectivité grâce à un dédoublement cinétique. L’accès à un large panel de molécules, ainsi qu’aux imines correspondantes via un mécanisme de rétro-Mannich par l’emploi d’une oléfine énolisable, démontre la robustesse de la réaction d’ortho CH-fonctionnalisation. La formation de liaison carbone-carbone par les métaux de transition a été largement développée depuis quelques décennies. Cependant elle génère souvent des déchets et l’utilisation de réactifs toxiques à haute température. La catalyse photorédox connaît un vif intérêt depuis peu et a l’avantage d’utiliser la lumière comme source d’énergie couplé à une faible quantité catalytique de métal ou d’organocatalyseur. Nous avons ainsi développé une méthode de couplage biaryalique via une catalyse photorédox médiée par un complexe de ruthénium. Les précurseurs à coupler que sont les arènes diazoniums ont l’avantage de ne générer comme déchets que du diazote, et réalise une réaction de substitution homolytique aromatique sur des accepteurs aromatiques ou hétéroaromatiques. De plus elle se déroule à température ambiante en l’absence de base. Elle constitue donc une alternative pour le couplage biarylique en une chimie éco-compatible. / Catalysis by transition metal has considerably grown these decades and has become a powerful tool in organometallic chemistry. The CH ortho fonctionnalisation reaction, involving a duale palladium/norbornene catalysis, discovered at the end of the 90’s, allowed a breakthrough in the field of multi-component reactions. It provides access to polycyclic structures through an original mechanism, involving a palladacycle formation. It is the first catalytic reaction including three oxidation states of palladium (0, II and IV). In a context where the chemistry is going to be more ecocompatible, we wished taking advantage of this reaction to synthetize dibenzoazepines. They represent interesting scaffold both as organocatalysts and as bioactive compounds, however the existing synthesis don’t allow diversifying the structure of these molecules and often requiring multi-step sequences or toxic reagents. Dibenzoazepines synthesis has been realised according a three components approach from readily available reagents, a bromobenzylamine, an ortho substituted aromatic iodide and an electrowithdrawing olefin via a CH ortho fonctionnlisation/Heck/aza-Michael sequence. Remarquably, this last step presents a total diastereoselectivity. Using racemic substituted bromobenzylamine shows the same selectivity thanks to a parallel kinetic resolution-like mechanism. The access to a wide range of molecules, and the corresponding imine via a retro-Mannich mechanism using an enolisable olefin demonstrates the robustness of the ortho CH fonctionnalisation reaction.  Carbon-carbon bond formation by transition metal has been largely developped since decades. However, it often generate waste and use toxic reagent at high temperature. Photoredox catalysis is a great success recently and have the advantage to use light as energy source and small amounts of metal and organocatalyst. We have developed a method of biarylic coupling via a photoredox catalysis mediated by a ruthenium complex. Arene diazonium, the precursor coupled, have the advantage to generate diazote as waste, and realise an homolytic aromatic substitution on aromatic and heteroaromatic acceptors. Moreover, it takes place at room temperature without base. It is an alternative for the biarylic coupling and an green chemistry.

Le travail réalisé dans cette thèse a consisté en deux parties principales; la première partie a été centrée sur l’isolement de métabolites marins bioactifs, en mettant l'accent sur l'utilisation de techniques intégrés et modernes pour l'exploration chimique de deux éponges marines sélectionnées pour leurs activités cytotoxiques et antiinfectieuses. L’inhibition du Quorum Sensing pour explorer les activités antibiofilms a été utilisée. L’étude chimique de la première éponge Monanchora sp., a permis l'isolement et l'identification de vingt-huit composés guanidiniques et polycycliques, dont onze nouveaux. De la deuxième éponge Suberea ianthelliformi, nous avons pu isolé et identifié douze métabolites de type bropmotyrosines incluant huit alcaloïdes nouveaux dont les tétrabromotyrosines de la famille psammaplysenes. Les composés isolés ont été évalués pour leurs activités biologiques, en particulier pour les activités ciblées, cytotoxicité et inhibition de quorum sensing (QSI). De nombreux composés se sont avérés cytotoxiques sur plusieurs lignées cellulaires cancéreuses à des concentrations allant du micro au nanomolaire, en particulier les produits pentacycliques de la famille des crambescidines 800 et 814 alcaloïdes (CI50 = 4.5 nM). Ces résultats sont présentés à la fin du manuscrit. La deuxième partie concerne la synthèse bioinspirée du fragment guanidinique et tricyclique central des crambescidines et batzelladines. La synthèse totale de deux analogues tricycliques de merobatzelladine B a été ainsi réalisée. La stratégie de synthèse est essentiellement basée sur une réaction bioinspirée et inspiré de la stratégie de Robinson lors de la synthèse de la tropénone. / The work achieved in this thesis consisted two main parts; the first part was centered to the l marine natural product program, with emphasis on using modern and integrated techniecs for the chemical exploration of two promising marine sponges for the discovery of new marine secondary metaboilites along with their biological evalutions as anticancers, antibiotics, antifouling and antibiofilms. The chemical exploration of the first marine sponge Monanchora sp., afforded the isolation and identification of twenty-eight compounds, included eleven new compounds. The second marine sponge Suberea ianthelliformis, we were able to isolate and identify twelve marine metabolites included four known compounds and eight new tetrabromo tyrosine alkaloids related to psammaplysenes family. The isolated compounds were evaluated for their biological activities, in particular for cytotoxicity, quorum sensing inhibition (QSI) and antibiofilms. Almost of the isolated compounds exhibited interesting high cytotoxic activity against several cancer cell lines ranging from micro to nanomolar scale, in particular the isolated pentacyclic crambescidin 800 and 814 guanidine alkaloids showed strong cytotoxicity with IC50 = 4.5 nM. The second part was concerning with the bioinspired synthesis of the central tricyclic guanidinic fragments of the polycyclic marine alkaloids, batzelladines/crambescidins, in addition to the total synthesis of two stereoisomeric analogues of merobatzelladine B tricyclic alkaloid. Successfully, we had achieved a four steps short stratgy to access the tricyclic guanidinic portion of the batzelladine alkaloids, based on a bioinspired Robinson multicomponant reaction.

Au cours de ce travail, nous avons abordé la synthèse biomimétique sous des angles variés. Une déclinaison des approches bio-inspirées a en effet permis de réaliser plusieurs synthèses totales d'alcaloïdes polycycliques complexes. La biogenèse des substances naturelles considérées est placée au centre de la démarche. Au départ, pour définir la stratégie de synthèse puis, en conclusion, lorsque les synthèses réalisées mènent a des hypothèses biosynthétiques plus abouties.Le squelette des drimentines, alcaloïdes hybrides possédant une partie sesquiterpénique, a été obtenu grâce à une séquence de désaromatisation-cyclisation qui mime l'étape-clé de la biogenèse de ces métabolites spécialisés.Une stratégie d'auto-assemblage par dimérisation a été adoptée afin d'étudier les liens synthétiques et biosynthétiques qui unissent les alcaloïdes marins de la famille des aplysinopsines. Au cours de cette étude, les premières synthèses totales du dictazole B et du tubastrindole B ont été réalisées. De plus, l'obtention d'analogues proches des substances décrites et d'un intermédiaire biogénétique supposé a permis de développer une hypothèse de biogenèse se fondant sur la spontanéité et les réactivités chimiques observés au cours de l'étude. L'application de la catalyse à l'ADN à ces travaux a également conduit à des résultats prometteurs.Enfin, une méthode bio-informatique récente appelée "molecular networking" peut être mise à profit afin d'exploiter la diversité de mélanges synthétiques complexes générés par la mise en présence de quelques précurseurs simples. La démarche s'applique à des mélanges connus dans lesquels la nitraramine ou la nitrarine se forment ainsi qu'à des mélanges inédits pouvant conduire, par exemple, au myrifabral A.Ces études montrent encore une fois que la synthèse biomimétique est un outil puissant pour la synthèse totale de substances naturelles polycycliques complexes et ce de bien des manières. On peut retenir que ces stratégies permettent d'accéder à des cibles extrêmement complexes avec simplicité, sobriété et élégance. / This work features various approaches of biomimetic organic syntheses. Biosynthetic considerations have been placed at the center of our analysis in order to define the synthetic plans and later to propose biosynthetic hypotheses.First, the skeleton of drimentines, hybrid alkaloids containing a sesquiterpenic unit, has been obtained by mimicking the main event of their postulated biosynthesis.In a wider study, the marine alkaloid family of the aplysinopsins has been treated with two total syntheses, of dictazole B and tubastrindole B, as well as a full bio-relevant aplysinopsins’ cascade and the application of DNA catalysis principles to the series.Finally, novel dereplication techniques relying on "molecular networking are currently tested on complex synthetic mixtures to merge one step total syntheses and diversity oriented synthesis.

Le but de ce travail de doctorat est l’étude chimique et biosynthétique de familles d’alcaloïdes guanidiniques d’origine marine provenant d’éponges de Méditerranée.Le travail est divisé en trois parties successives : 1) l’isolement d’alcaloïdes produits par des éponges marines de l’ordre des Poeciloscerida; 2) l’élucidation de la biosynthèse de la crambescine C1 par des études in vivo d’incorporation de précurseurs marqués au 14C; 3) la synthèse biomimétique de la crambescine A2 448 et de dérivés proches.La famille des alcaloïdes guanidiniques cycliques des crambescines est au coeur de la thèse, ces substances naturelles sont produites par l’éponge incrustante Crambe crambe. Ces alcaloïdes ont été découverts dans les années 1990 et ont suscité beaucoup d’intérêt pour leurs propriétés biologiques et écologiques et leurs synthèses totales. Par contre, leur biosynthèse était encore inconnue à ce jour. La seule synthèse biomimétique disponible était basée sur une hypothèse d’origine polyacétique. Les hypothèses récentes de nos groupes ont permis de mettre en avant une origine mixte: la partie cyclique guanidinique proviendrait d’un pyrrolidinium issu de l’arginine et d’un précurseur “céto-acide” proche des acides gras. Sur la base de cette hypothèse, nous avons mis au point une expérience d’incorporation qui a ensuite inspirée une voie de synthèse biomimétique pour l’accès aux crambescines et dérivés. Les premières conclusions quant à l’origine biosynthétique de ces molécules sont les faits les plus marquants de ce travail. Nous apportons une meilleure compréhension de la biochimie des alcaloïdes guanidiniques marins de structures complexes. / This thesis aims at the study of the chemical and biogenetic origin of specialized guanidine-alkaloid metabolites produced by sponges from the Mediterranean Sea.The work is divided into three main parts: 1) isolation of alkaloids produced by sponges of the Poeciloscerida order; 2) biosynthesis of crambescin C1 by in-vivo 14C-feeding experiments with Crambe crambe sponge; 3) biomimetic synthesis of crambescin A2 448 and derivatives. The main focus of the thesis will be the family of cyclic-guanidine alkaloids "crambescins", produced by the red incrusting sponge Crambe crambe.These alkaloids were discovered in the early 90s and despite the large interest on their biological activities, ecological roles, and synthesis, their biosynthesis is still unknown.The only available biomimetic synthesis of crambescins was based on a fully polyketide origin hypothesis. Recently our groups suggested an alternative biosynthetic hypothesis in which the guanidine-core would be originated from a condensation between a guanidinated pyrrolidinium derived from arginine and a beta-keto fatty acid. Based on this hypothesis, we designed a biosynthesis experiment that inspired a biomimetic synthesis route to access the crambescins and derivatives. The insights from these studies are the first experimental conclusions about the biosynthesis of crambescins. Finally, this work leads to a better comprehension of the biochemistry involved in guanidine marine alkaloids of complex structures.

Eco- Bite es un proyecto innovador que se enfoca en un estilo de vida saludable, complementando su idea de negocio para poder brindar un producto que aportará con la reducción de la contaminación ambiental. La idea de negocio propuesta es un producto práctico de transportar ya que se presentará mediante frascos de pastillas que a la vez serán reutilizables gracias a las recargas periódicas de acuerdo al consumo del cliente. Este producto está elaborado con insumos libres de químicos lo que evitará dañar nuestra salud bucal y aportar al cuidado, limpieza y blanqueamiento de los dientes. Las pastillas dentales Eco Bite está dirigida a personas de 18 a 55 años de nivel socio económico A y B zona 6, 7 y 8 (San Isidro, Miraflores, Surco, San Borja, La Molina. Eco- Bite será distribuido a través de tiendas multimarca ecológicas- naturales, ferias ecológicas donde se realizarán los lanzamientos de nuevas promociones, así como de manera virtual a través de las redes sociales más comerciales. La sede principal de Eco Bite Operará en el distrito de Lince donde funcionarán las áreas de producción, almacén y la oficina administrativa. Nuestra principal comunicación con nuestros futuros clientes será por redes sociales a través de la cual se mostrarán los atributos, beneficios y propiedades de las pastillas dentales, además de lanzamiento de nuevas promociones generando el interés para nuestros clientes. El producto Eco Bite no sólo se encargará del cuidado de salud bucal sino que además estará enfocado en la reducción de plásticos y microplásticos, aportando al cuidado del planeta. / Eco - Bite is an innovative project that focuses on a healthy lifestyle, complementing their business idea in order to provide a product that will contribute to reducing environmental pollution. The proposal of this business idea is a practical product of transport that will be presented by bottles of pills that will simultaneously be reusable thanks to the periodic charges according to consumption of the client. This product is made from chemical-free inputs which will prevent damage our oral health and they will contribute to the care, cleaning, and whitening of the teeth. Dental pills, Eco Bite is aimed at people 18 to 55 years of socio-economic level A and B from the zone 6, 7 and 8 (San Isidro, Miraflores, Surco, San Borja, La Molina). Eco - Bite will be distributed through multi-brand shops, eco - natural, ecological fairs where there will be launches of new promotions, as well as virtually through most commercial social networks. The Eco Bite headquarters operates in the Lince district where the production, warehouse and administrative office will operate. Our main communication with our future clients will be through social networks in which we displayed attributes, benefits, and properties of the dental pills, as well there we will launch new promotions generating interest from our clients. Product Eco Bite will not only take care of oral health care, but it will also focus on the reduction of plastics and microplastics, contributing to the good care of the planet. / Trabajo de investigación

El consumo de cremas productos de cuidado facial ha aumentado con el paso de los años. La creciente demanda por productos naturales ha ocasionado que diversas empresas opten por desarrollar nuevas propuestas de oferta para satisfacer dicha demanda. Debido a ello, la industria de cuidado facial se ha visto en la mira de las empresas para producir nuevos productos a base de insumos naturales. Por ello, se ha convenido en desarrollar una línea de producto de cuidado facial para satisfacer a la creciente demanda existente. Nuestra propuesta de trabajo es el desarrollo de una línea de productos de cuidado facial SkyGlad, la cual está dirigida a aquellas personas que buscan cuidar su piel, limpiar impurezas, hidratarla y tonificarla. El insumo fundamental de esta nueva línea de productos es el té verde. Este ofrece diversos beneficios para la piel, por ser un poderoso antioxidante, útil para tratar el acné, espinillas y eccema. Además, rejuvenece las células de la piel y alcanza una limpieza total, eliminando de todo tipo impurezas. De igual forma, cuenta con diversas esencias especiales beneficiosas para la piel. Son tres los productos a comercializar: Jabón, Crema Hidratante y Exfoliante. En el mercado actual, existen productos que cuentan con las mismas características del producto a elaborar, sin embargo; el producto propuesto se diferencia por el insumo característico: “té verde” y por los bajos niveles químicos. / The consumption of facial care products has increased over the years. The growing demand for natural products has caused various companies to choose to develop new supply proposals to meet this demand. Because of this, the facial care industry has been targeted by companies to produce new products based on natural inputs. Therefore, it has been agreed to develop a product line of facial care to meet the growing demand. Our work proposal is the development of a SkyGlad facial care products line, which is dedicated for those who really take care of their skin, clean impurities, moisturize and tone it. The fundamental input of this new product line is green tea. It offers various benefits for the skin, being a powerful antioxidant, useful for treating acne, pimples and eczema. In addition, it rejuvenates the skin cells and reaches a total cleaning, eliminating all kinds of impurities. Similarly, it has several special essences beneficial to the skin. There are three products to market: Soap, Moisturizing Cream and Exfoliating. In the current market, there are products that have the same characteristics of the product to be manufactured, however; SkyGlad product line has a differentiation guide by the characteristic input: "green tea" and by the low chemical levels. / Trabajo de investigación

<p>Juglone is a 1,4-naphthoquinone (1,4-NQ) and the allelochemical responsible for the well-known toxic effects of black walnut (<i>Juglans nigra</i>)<i> </i>and other members of the Juglandaceae. Juglone affects a variety of weed species via a mode of action unlike any commercially available herbicides, and thus has the potential to be used as a new natural product-based herbicide. However, lack of knowledge about its metabolism precludes introducing juglone biosynthesis traits into resistant crops through biotechnology. Herein, we established that juglone is derived from the phylloquinone pathway at the level of the intermediate 1,4-dihydroxy-2-naphthoic acid (DHNA). Phylloquinone is a primary 1,4-NQ made by all plants for photosynthetic electron transport. Despite the fundamental importance of phylloquinone, there are still unanswered questions about the subcellular architecture of the phylloquinone pathway. In chapter 3, we show that <i>o</i>-succinylbenzoate CoA-ligase is localized to both chloroplasts and peroxisomes and that its activity is vital in both organelles. The required dual localization of CoA ligase activity is a theme common to other plant pathways with CoA metabolic steps occurring in peroxisomes and thus leads us to propose a revised model of the phylloquinone pathway. Lastly, given the potential of introducing juglone biosynthesis as part of novel weed management strategies, we investigated the circumstances, costs, and benefits of producing allelochemicals in crops using an evolutionary game theory model. Together, this work (i) shows that the phylloquinone pathway provides crops with the biosynthetic framework to produce juglone, (ii) sheds new light on the phylloquinone pathway architecture, and (iii) reveals the circumstances in which producing an allelochemical will be an evolutionarily stable strategy. We envision these results will assist biotechnological efforts to utilize juglone as a novel, natural product-based herbicide.</p>

The use of plants for cosmeceutical applications is becoming more important since “safer” and more “natural” skin products are gaining popularity. The effect of different drying methods and storage conditions on metabolite changes and biological activity of two species with cosmeceutical application namely Greyia flanaganii and Leucosidea sericea were investigated using 1H-NMR metabolomics. The multivariate analysis (PCA and OPLS-DA), and 1H-NMR sample spectra were used to analyse the significant differences (P<0.05) resulting from the different treatments. The effect of these treatments on anti-tyrosinase and anti-bacterial (against Staphylococcus aureus) activity of G.flanaganii and L.sericea ethanol leaf extracts respectively, was further investigated to assess the quality. Four different drying methods adopted were freeze drying, oven drying at 50°C, air drying at room temperature and sun drying in a greenhouse. The dried leaf extracts were stored in three different conditions of fridge, freezer and shade conditions and samples from each storage condition taken for analysis at three and six months of storage. The chemical constituents of the leaf extracts of both species were not affected by the drying method and the storage condition, but the concentrations of the metabolites changed. The treatments did not show a significant difference (P<0.05) on the biological activity of the extracts. However, G.flanaganii plant material harvested from the University of Pretoria exhibited a higher anti-tyrosinase activity than material harvested from Mothong heritage site. In G. flanaganii freshly freeze and oven dried extracts exhibited a higher anti-tyrosinase activity with fifty percent inhibitory (IC50) activity of 16.8±0.69 μg/ml and 15.73±0.85 μg/ml respectively than the activity of sun and air dried with IC50 values of 33.08±0.78 μg/ml and 36.86±2.01 μg/ml respectively. The metabolite concentrations and anti-tyrosinase activity dropped significantly after storage. Leucosidea sericea oven and freeze dried extracts, exhibited good anti-bacterial activity with a minimum inhibitory concentration (MIC) value of 0.25 μg/ml and 0.125 μg/ml respectively as compared to sun and air dried extracts with the same MIC value of 0.5 μg/ml. Freeze dried samples showed the best anti-bacterial activity (MIC 0.125 μg/ml) compared to other drying methods. Fridge and freezer storage conditions enhanced the activity of stored sample. / College of Agriculture and Environmental Sciences / M. Sc. (Agriculture)

The diploma thesis focuses on analysis of fatty alcohols with mass spectrometry. Theoretical part describes distribution, main properties, usage and analytical methods for analysis of fatty alcohols. Experimental work focuses on the search for a proper derivatisation procedure for fatty alcohols, which would enable their detection with soft ionisation techniques of mass spectrometry, as well as their structural analysis. The main aim of the structural analysis is to find the methyl branching in the fragmentation spectra of derivatives of the fatty alcohols.

>Magister Scientiae - MSc / The high rate of rediscovery of known compounds has led to a decline in the discovery of novel natural products. The high biodiversity of organisms growing in extreme conditions such as oceans has led to the increased interest by researchers for their use as a source of novel natural products. Marine bacteria are known for their extensive biosynthetic capacity to produce diverse natural products, which are suitable for various biotechnology applications such as in agriculture, for treatment of fungal plant pathogens, and as antibiotics, for treatment of bacterial infections. This study aimed at discovering novel secondary metabolites from marine bacteria previously associated with novel marine invertebrate species endemic to the South African coast. The methodologies used in this study included a bioassay guided fractionation coupled to genome sequencing and mining. For the bioassay guided fractionation approach, the study first focused on screening marine bacteria for antimicrobial activity when cultured on 4 different media, against fungal strains previously shown to be virulent olive trunk pathogens. In parallel, the bacterial isolates with the most inhibitory activity against the fungal pathogens were also screened for antimicrobial activity against 4 indicator strains including Gram-negative Escherichia coli 1699 (E. coli), Pseudomonas putida, and Gram-positive Staphylococcus epidermidis ATCC14990, and Bacillus cereus ATCC10702. One of the marine bacterial isolates, PE6-126, showed diverse antimicrobial activity including antibacterial and antifungal activity against the tested strains. The genome sequencing data revealed that this isolate was B. cereus based on the average nucleotide identity (ANI) (>99%) to reference strains. antiSMASH analysis of the genome revealed nine predicted secondary metabolite clusters including bacteriocins (2), non-ribosomal peptide synthetase (NRPS) (2), siderophore (1), sactipeptide (1), betalactone (1), linear azol(in)e-containing peptides (LAP) - bacteriocin (1) and a terpene (1). Some of these pathways had low to no sequence similarity to known pathways, indicating the potential of these pathways to produce novel compounds. One of the pathways showed very high sequence similarity to the thuricin CD pathway in Bacillus thuringiensis. Considering that thuricin CD has been reported to have antimicrobial activity against B. cereus (ATCC1072), it was hypothesised that it could also be produced by PE6-126. However, the antimicrobial extract from PE6-126 was tested for sensitivity to proteinase K and heat treatment, which thuricin CD is known to be sensitive to. The results revealed that the antimicrobial activity was not lost after treatment, implying that a different metabolite could be responsible for the anti-B. cereusactivity. In addition, PE6-126 initially displayed antimicrobial activity against a multi-drug resistant E. coli 1699, suggesting some of the antimicrobial compound/(s) produced by this strain could potentially be novel. The bioassay-guided fractionation approach coupled to Liquid Chromatography Mass Spectrometry (LC-MS) did not lead to identification of the antimicrobial compound/(s), therefore it remains a question whether the secondary metabolite pathways predicted by antiSMASH lead to the production of the active compound/(s).The results from this study showed that even well studied species have the potential to synthesize as yet undescribed compounds, based on the novelty of some of the pathways. This study highlights the importance of employing a genome-guided approach in drug discovery, as there may be many novel compounds to discover from biosynthetic pathways that have not yet been characterised. Further research is needed to identify the antimicrobial compound/(s) produced by PE6-126.