Compounds and uses thereof

Abstract

The invention relates to a compound of formula (I), a composition comprising the compound of formula (I) and a use of the compound of formula (I) as an antimicrobial agent. The invention also relates to a compound of formula (I) for use in treating a bacterial disease or infection in a subject, a method for treating a plant to control a disease, and a method for producing a compound of formula (I).

Description

[0001] COMPOUNDS AND USES THEREOF

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a compound of formula (I), a composition comprising the compound of formula (I) and a use of the compound of formula (I) as an antimicrobial agent. The invention also relates to a compound of formula (I) for use in treating a bacterial disease or infection in a subject, a method for treating a plant to control a disease, and a method for producing a compound of formula (I).

[0004] BACKGROUND

[0005] Antimicrobial compounds are a large group of compounds known for stopping or preventing the growth and spread of a range of microorganisms. Therefore, antimicrobials play a significant role in the fight against pathogenic diseases in plants, animals and humans.

[0006] Antibacterial compounds are antimicrobials that are used to treat or control diseases or infections caused by bacteria. Therefore, this group of compounds finds applications across many medical and biotechnological fields. For example, they can be used to treat infections caused by opportunistic bacterial pathogens that target immunocompromised subjects.

[0007] Antifungal compounds are another type of antimicrobials that are generally used to treat or control diseases or infections caused by fungi or fungi-like microorganisms. Antifungal compounds are particularly known for their use in treating or preventing plant diseases that affect the growth and quality of food crops.

[0008] Amongst the most popular food crops are cereals, such as wheat, potato and tomato. Out of over 200 diseases of wheat, 50 cause economic losses and are widely distributed. Each year, about 20% of wheat is lost due to diseases, with some diseases responsible for up to 50% yield loss. Some major wheat diseases are rusts, smut, tan spot, spot blotch, fusarium head blight, common root rot, septoria blotch, powdery mildew, blast, and several viral, nematode, and bacterial diseases.

[0009] 17208777 CXB CXB Similarly , potato and tomato crops are affected by an array of diseases. For example, some of the most important diseases affecting potato crops worldwide include late blight, early blight, stem canker, potato wart, powdery scab, bacterial wilt, black leg, potato virus Y (PVY), potato leaf roll virus and yellow potato cyst nematode. Some of these diseases also affect tomatoes such as late blight and early blight. Additionally, tomato crops are affected by diseases such as buckeye rot, anthracnose, and tomato spotted wilt. These plant diseases cause mortality of the plant and thereby negatively impact the quality and yield of the plants.

[0010] Reduced crop yield leads to higher crop prices for consumers and could lead to reduced regional food security. Thus, there is a need for a better disease control of plants, including wheat, potato and tomato.

[0011] Hospital acquired infections are becoming increasingly common and pose a serious risk to patients, staff and visitors. These infections are usually caused by antibiotic resistant bacterial strains such as MRSA and C. difficile. Therefore, there is an ongoing need to supply new antibacterial agents effective against bacteria present in the hospital and healthcare setting.

[0012] Bacterial and fungal infections in human or animal subjects are especially common in immunocompromised individuals. This includes hospital patients, and particularly, individuals receiving immunosuppressive therapy for autoimmune or neoplastic disease, organ transplant recipients and AIDS patients. Other immunocompromised individuals susceptible to opportunistic bacterial or fungal pathogens include combat troops / soldiers and individuals exposed to conflict or war zones. As these individuals are more prone to infection and struggle to fight the infection, a need exists for an effective compound for treating a bacterial or fungal disease.

[0013] Bacteria produce different compounds which might find therapeutic or industrial applications. For example, Bacillus species are known to produce compounds of antibacterial and antifungal activity, such as Mersacidin, Pumilin, or Mycosubtilin. Thus, bacteria can provide a source of new antibacterial and antifungal compounds.

[0014] It is one object of the present invention to overcome at least some of the disadvantages of the prior art or to provide a commercially useful alternative thereto.

[0015] 17208777 CXB CXB It is a further object of the invention to provide a compound that shows antimicrobial properties such as antifungal and / or antibacterial properties.

[0016] It is a further object of the invention to provide a compound that can be used to treat a bacterial or fungal infection or disease, especially in immunocompromised subjects such as hospital patients and individuals exposed to war or conflict zones.

[0017] It is a further object of the invention to provide a compound that can be used to treat or control fungal diseases or infections in plants such as wheat, tomato and potato crops.

[0018] SUMMARY OF THE INVENTION

[0019] In a first aspect the invention provides a compound of formula (I): wherein R1is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0020] R2is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group; wherein R12is selected from -H and -OH, and n is selected from 0 to 3;

[0021] R4is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0022] R5is or tautomers thereof, wherein m is selected from 1 to 5;

[0023] R6is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0024] R7is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0025] 17208777 CXB CXB R8is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0026] R9is selected from wherein R13is selected from -H and Ci-Ce-alkyl, and p is selected from 1 to 5;

[0027] R10is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0028] R11is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl.

[0029] In a second aspect, the invention provides a composition comprising the compound of the first aspect, and optionally, an acceptable carrier or excipient (e.g. a pharmaceutically acceptable carrier).

[0030] In a third aspect, the invention provides a use of the compound of the first aspect or the composition of the second aspect as an antimicrobial agent. The antimicrobial agent may be an antifungal agent or an antibacterial agent. In some embodiments, the antifungal agent may be an anti-yeast agent. The antimicrobial agent may be used to treat plants.

[0031] In a fourth aspect, the invention provides the compound of the first aspect or the composition of the second aspect for use in treating a bacterial disease or infection in a subject. Preferably, the subject is human.

[0032] In a fifth aspect, the invention provides a method for treating a plant to control a disease, the method comprises applying an effective amount of the compound of the first aspect or the composition of the second aspect to the plant or a part of the plant.

[0033] In a sixth aspect, the invention provides a method for producing a compound of formula (I) comprising synthesising the compound of formula (I) from a biosynthetic gene cluster expressing the proteins of SEQ ID NOs: 1-31 or proteins of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31.

[0034] 17208777 CXB CXB The invention also provides the biosynthetic gene cluster encoding any one of the peptides of SEQ ID NOs: 1-31, or peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31. The biosynthetic gene cluster may encode at least 10, at least 20, at least 30, or all of the peptides of SEQ ID NOs: 1-31, or peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31.

[0035] Other preferred embodiments of the compounds according to the invention appear throughout the specification and in the examples.

[0036] Without wishing to be bound by a particular theory, the antimicrobial properties of the compound of formula (I) might be the result of its ability to sequester iron into an iron- compound (I) complex, which depletes the iron pool. If the microbe lacks a transporter for compound of formula (I), the iron-compound (I) complex remains inaccessible, driving iron starvation and growth inhibition.

[0037] In the embodiments in which the compound of formula (I) forms (or is) a siderophore, the antimicrobial properties are especially prevalent when: (i) the compound of formula (I) has greater thermodynamic Fe(lll) affinity and sufficient kinetic stability compared with the pathogen’s native siderophore(s), (ii) environmental iron is limiting, and / or (iii) the pathogen cannot hijack the compound of formula (I) via compatible uptake receptors. Under conditions of limited iron in the environment, many pathogens depend on siderophores for Fe(lll) uptake. Thus, the compound of formula (I) might have a higher affinity for Fe(lll) than the native siderophores of the microbe. Native siderophores may be derived from the non- ribosomal peptide synthetase (NRPS)-dependent siderophore pathway or the NRPS- independent siderophore (NIS) synthetase. Examples of native siderophores include hydroxamates, such as desferrioxamine, and catecholates, such as enterobactin.

[0038] Other modes of action of the compound of formula (I) may include direct oxidative stress, cell membrane disruption, quorum sensing interference, induced systemic resistance in plants, biofilm inhibition and / or enzyme inhibition by metal removal.

[0039] The compound of formula (I) is effective against many pathogens. That is to say that the compound of formula (I) may, for example, inhibit the growth of many pathogens. Preferably, the compound of formula (I) is effective against microbes (e.g. fungi and / or bacteria) that rely on iron for survival and / or growth. Thus, the compound of formula (I) may

[0040] 17208777 CXB CXB be effective against microbes (e.g. fungi and / or bacteria) that produce siderophores (i.e. small molecules that chelate iron to make it available for uptake). The compound of formula (I) may be effective against iron-scavenging microbes. The compound of formula (I) may be effective against iron-scavenging bacteria. The compound of formula (I) may be effective against iron-scavenging fungi. That is to say that the compound of formula (I) may be used to treat diseases caused by iron-scavenging microbes (e.g. bacteria or fungi). The compound of formula (I) may be used to inhibit the growth of iron-scavenging microbes (e.g. bacteria or fungi).

[0041] It will be understood that iron-scavenging microbes (and bacteria and / or fungi) refers to microorganisms that utilise or produce siderophores for iron uptake, microorganisms that exhibit siderophore-mediated iron acquisition pathways, and / or microorganisms that depend on siderophores for growth and survival.

[0042] The compound of formula (I) may also be effective against microorganisms devoid of siderophore systems, but which are reliant on extracellular iron pools vulnerable to siderophore sequestration.

[0043] The inventors of the present application have shown that compound of formula (I) has antimicrobial properties, particularly, antifungal and antibacterial properties. Compound of formula (I) may be used to treat plant and / or animal diseases. Compound of formula (I) may be used to treat diseases caused by bacterium, fungus and / or yeast. Specifically, compound of formula (I) is effective in treating infections or diseases caused by plant pathogens, such as Zymoseptoria tritici and Phytophthora infestans as well as human or animal pathogens, such as Acinetobacter baumannii. The inventors of the present application have also shown that compound of formula (I) has antimicrobial properties against Venturia inaequalis, Microdochium nivale, Botrytis cinerea, Verticillium dahliae, and Phytophthora cactorum. In addition, compound of formula (I) was shown to inhibit the growth of Cryptococcus neoformans, Candida krusei, Klebsiella pneumoniae and Staphylococcus aureus. Therefore, compound of formula (I) has applications in the medical and biotechnology fields. Compound of formula (I) is particularly suitable for use in therapy and for controlling plant and / or animal diseases.

[0044] The present inventors have surprisingly discovered that compound of formula (I) is effective as an antibacterial agent, for example, against Acinetobacter baumannii, a gram-negative

[0045] 17208777 CXB CXB bacterium which can act as an opportunistic pathogen in animals and humans, primarily affecting individuals with compromised immune systems. The present inventors have surprisingly discovered that compound of formula (I) is effective as an antibacterial agent, for example, against Klebsiella pneumoniae, a gram-negative bacterium which can cause pneumonia, or a urinary tract infection. The present inventors have surprisingly discovered that compound of formula (I) is effective as an antibacterial agent, for example, against Staphylococcus aureus a gram-positive bacterium which can cause respiratory tract or skin infections.

[0046] The present inventors have surprisingly discovered that compound of formula (I) is effective as an antifungal agent, for example, against Zymoseptoria tritici, a wheat plant pathogen causing septoria leaf blotch and against Phytophthora infestans, a potato and tomato plant pathogen causing late blight or potato blight. Compound of formula (I) is also effective as an antifungal agent, for example, against Venturia inaequalis (i.e. an ascomycete fungus that causes the apple scab disease), Microdochium nivale (a fungus causing Fusarium patch in turf grass and seedling blight, foot and root rot, and ear blight in wheat), Botrytis cinerea (i.e. a necrotrophic fungus that affects many plant species, including wine grapes), Verticillium dahliae (i.e. a fungal plant pathogen, which causes leaves to curl and discolour), and a fungal-like pathogen Phytophthora cactorum (which may cause root rot on many plant species and leather rot of strawberries).

[0047] The present inventors have surprisingly discovered that compound of formula (I) is effective as an agent against yeast, for example, against Cryptococcus neoformans (which can cause diseases in plants and humans, especially in immunocompromised humans), and Candida krusei (i.e. a budding yeast).

[0048] Each aspect or embodiment as defined herein may be combined with any other aspect(s) or embodiment(s) unless clearly indicated to the contrary. In particular any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

[0049] DETAILED DESCRIPTION OF THE INVENTION

[0050] Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of

[0051] 17208777 CXB CXB ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the event of any latent ambiguity, definitions provided herein take precedence over any dictionary or extrinsic definition.

[0052] As used in the specification and the appended claims, unless specified to the contrary, the following terms have the meaning indicated:

[0053] As used herein, singular prepositions such as “a,” “an,” and “the,” are often used for convenience, however, all instances of the singular are intended to encompass the plural unless otherwise indicated either explicitly or from context. The terms “comprising”, “including” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements. Further, it should be understood that all references, including journal articles, books, patents, technical documents, and the like, mentioned in this disclosure are hereby incorporated by reference in their entirety and for all purposes.

[0054] As used herein, the term “independently selected” means that each R group, such as R1, R2, R3, can be identical or different. For example, the expression “R1, R2or R3are independently selected from -H and Ci-Ce-alkyl” means, for example, that each R1, R2or R3may be a Ci-Ce-alkyl or R1and R3may be a Ci-Ce-alkyl and R2an -H atom.

[0055] As used herein, the term “hydrocarbyl” group (alone or in combination with another term(s)) means a straight-or branched-chain hydrocarbon radical typically containing 1 to 15 carbon atoms such as 1 to 10, 1 to 8, 1 to 6, or 1 to 4 carbon atoms. Attachment to the hydrocarbyl group occurs through a carbon atom. A “Cnhydrocarby group refers to an aliphatic radical containing n carbon atoms. For example, a Ci-Ce hydrocarbyl group contains 1 , 2, 3, 4, 5, 6 carbon atoms. The “hydrocarbyl” group may be a substituted or unsubstituted “alkyl” or “alkenyl” group. For example, “Ci-Ce-hydrocarbyl” means a straight or branched aliphatic radical having 1 to 6 carbon atoms such as a “Ci-Ce-alkyl” or a “Ci-Ce-alkenyl”, optionally substituted with a -OH group. As used herein, the term “Ci-Ce-hydrocarbyl substituted with at least one -OH” group means a straight-or branched-chain aliphatic radical having 1 to 6 carbon atoms in which one of the -H atoms bonded to a carbon atom is replaced with an - OH group. Preferably, the Ci-Ce-hydrocarbyl substituted with at least one -OH group is Ci- Ce alkyl.

[0056] 17208777 CXB CXB As used herein, the term "alkyl” group (alone or in combination with another term(s)) means a straight-or branched-chain saturated radical typically containing 1 to 15 carbon atoms, such as 1 to 10, 1 to 8, 1 to 6, or 1 to 4 carbon atoms. A “Cnalkyk group refers to an aliphatic radical containing n carbon atoms. For example, a C1-C10 alkyl group contains 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. Attachment to the alkyl group occurs through a carbon atom. The alkyl group may comprise methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl (branched or unbranched), hexyl (branched or unbranched), heptyl (branched or unbranched), octyl (branched or unbranched), nonyl (branched or unbranched), or decyl (branched or unbranched) group(s). The “alkyl” group may optionally be substituted with at least one group selected from -OH, halo (e.g. a fluorine, chlorine, bromine, or iodine atom), formyl or acetyl. For example, the term “Ci-Ce- alkyl” means a saturated straight or branched aliphatic radical having 1 to 6 carbon atoms and optionally substituted with an -OH group. As used herein, the term “Ci-Ce-alkyl substituted with at least one -OH” group means a straight-or branched-chain saturated aliphatic radical having 1 to 6 carbon atoms in which one of the -H atoms bonded to a carbon atom is replaced with an -OH group.

[0057] As used herein, the term "alkenyl" group (alone or in combination with another term(s)) means a straight-or branched-chain hydrocarbon substituent containing one or more double bonds and typically 2 to 15 carbon atoms; such as 2 to 10, 2 to 8, 2 to 6 or 2 to 4 carbon atoms. Attachment to the alkenyl group occurs through a carbon atom. The “alkenyl” group may comprise ethenyl (vinyl), 1-propenyl, 3-propenyl, 1,4-pentadienyl, 1 ,4- butadienyl, 1-butenyl, 2-butenyl, 3-butenyl, pentenyl and hexenyl. The “alkenyl” group may optionally be substituted with at least one group selected from an -OH or halo group (e.g. a fluorine, chlorine, bromine, or iodine atom). For example, the term “Ci-Ce-alkenyl” means an unsaturated straight or branched aliphatic radical having 1 to 6 carbon atoms and optionally substituted with an -OH or halo group. As used herein, the term “Ci-Ce-alkenyl substituted with at least one -OH” group means a straight-or branched-chain unsaturated aliphatic radical having 1 to 6 carbon atoms in which one of the -H atoms bonded to a carbon atom is replaced with an -OH group.

[0058] As used herein, the term “antimicrobial” in the context of uses and / or agents is intended to encompass uses and agents that, upon administration or application to a plant or subject, result in the prevention or inhibition of microbial growth. The term “antimicrobial” relates to compounds (such as a compound of formula (I)) which are active against microbes.

[0059] 17208777 CXB CXB Microbes include microorganisms such as fungi, fungi-like microorganisms (e.g. Oomycota or water mold), mold and bacteria. The administration or application of antimicrobial agents may result in microbial death or growth inhibition. Preferably, antimicrobial agents are selective against fungal or fungal-like pathogens and / or bacterial pathogens. The subject may be an animal or human suffering from a microbial disease or infection.

[0060] As used herein, the term “antifungal” in the context of uses and / or agents is intended to encompass uses and agents that, upon administration or application to the plant or subject (e.g. human), result in the prevention or inhibition of fungal growth. The term “antifungal” relates to the application or administration of compounds (such as a compound of formula (I)) which are active against fungi (especially against fungal pathogens). The administration or application of antifungal agents may result in fungal death or growth inhibition. The antifungal agent may be selective for fungal pathogens such as Zymoseptoria tritici, Aspergillus fumigatus, Venturia inaequalis, Microdochium nivale, Botrytis cinerea, and / or Verticillium dahliae. Compound of formula (I) may have specificity for fungal pathogens over, for example, other microbial pathogens.

[0061] The term “fungi” or “fungal” is intended to cover fungi as well as fungi-like microorganisms such as Oomycota, Water mold and / or yeast. Preferably, fungi-like microorganisms include Peronoporales, more preferably, fungi-like microorganisms belong to the Peronosporaceae family, more preferably fungi-like microorganisms have the genus Phytophthora, more preferably the fungi-like microorganism is Phytophthora infestans and / or Phytophthora cactorum. The yeast may be Cryptococcus neoformans and / or Candida krusei. Therefore, antifungal in the context of uses and / or agents is also intended to encompass uses and agents that, upon administration or application to the plant, result in the prevention or inhibition of the growth of fungi-like microorganisms.

[0062] As used herein, the term “antibacterial” in the context of uses and / or agents is intended to encompass uses and agents that, upon administration or application to the subject, result in the prevention or inhibition of bacterial growth. The term “antibacterial” relates to the application or administration of compounds (such as a compound of formula (I)) which are active against bacteria (especially against pathogenic bacteria). The administration or application of antibacterial agents may result in bacterial death or growth inhibition. The antibacterial agent may be selective for bacterial pathogens, such as Acinetobacter baumannii, Klebsiella pneumoniae, and / or Staphylococcus aureus. Compound of formula

[0063] 17208777 CXB CXB (I) may have specificity for bacterial pathogens over, for example, other microbial pathogens. The subject may be an animal or human. The subject may be an animal or human suffering from a bacterial disease or infection. Preferably, the subject is an individual with a compromised immune system, such as a subject suffering from HIV / AIDS, a hospital patient, a member of combat troops or an individual exposed to war or conflict zones.

[0064] The expression “control a disease” as used herein (in the context of methods and uses of the invention) is intended to encompass inhibition of the progression of the disease and / or treatment of the disease. That is to say that compound of formula (I) may stop the disease from progressing or may reverse the effects of the disease. The disease may be a fungal or bacterial disease.

[0065] The compounds of the present invention may possess some aspect of stereochemistry. For example, the compounds may possess chiral centres and I or planes and I or axes of symmetry. As such, the compounds may be provided as single stereoisomers, single diastereomers, mixtures of stereoisomers or as racemic mixtures. Stereoisomers are known in the art to be molecules that have the same molecular formula and sequence of bonded atoms, but which differ in their spatial orientations of their atoms and I or groups.

[0066] In addition, the compounds of the present invention may possess tautomerism. Each tautomeric form is intended to fall within the scope of the invention.

[0067] The invention provides a compound of formula (I): wherein R1is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0068] R2is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0069] R3is wherein R12is selected from -H and -OH, and n is selected from 0 to 3;

[0070] 17208777 CXB CXB R4is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0071] R5is or tautomers thereof, wherein m is selected from 1 to 5;

[0072] R6is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0073] R7is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0074] R8is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0075] R9is selected from wherein R13is selected from -H and Ci-Ce-alkyl, and p is selected from 1 to 5;

[0076] R10is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0077] R11is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl.

[0078] R1, R2and R8may be independently selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group. The Ci-Ce-hydrocarbyl group may include Ci-Ce- alkyl and Ci-Ce-alkenyl. The Ci-Ce-alkyl and Ci-Ce-alkenyl may be optionally substituted with at least one -OH group. Preferably, the Ci-Ce-hydrocarbyl may be a Ci-Ce-alkyl, optionally substituted with at least one -OH group, or a Ci-Ce-alkenyl.

[0079] In one embodiment, R1, R2and R8may be independently selected from -H and Ci-Ce- hydrocarbyl optionally substituted with one -OH group. The Ci-Ce-hydrocarbyl group may include Ci-Ce-alkyl and Ci-Ce-alkenyl. The Ci-Ce-alkyl and Ci-Ce-alkenyl may be optionally substituted with one -OH group. Preferably, the Ci-Ce-hydrocarbyl may be a Ci-Ce-alkyl, optionally substituted with one -OH group, or a Ci-Ce-alkenyl.

[0080] 17208777 CXB CXB In a preferred embodiment, the Ci-Ce-hydrocarbyl is a Ci-Ce-alkyl. The Ci-Ce-alkyl includes saturated straight or branched hydrocarbon radicals having from 1 to 6 carbon atoms. For example, R1, R2and R8may be independently selected from -H, methyl, ethyl, propyl, butyl, pentyl and hexyl, 2-methylpropyl, 2-methylbutyl, 3-methylbutyl, 2-ethylbutyl, 3-ethylbutyl, 2- methylpentyl, 3-methylpentyl or 4-methylpentyl. Preferably, the Ci-Ce-alkyl is selected from methyl, ethyl, propyl and 2-methylpropyl.

[0081] In a further preferred embodiment, R1, R2and R8may be independently selected from -H and Ci-Cs-alkyl. R1, R2and R8may be independently selected from -H and Ci-C4-alkyl. R1, R2and R8may be independently selected from -H and Ci-Cs-alkyl. Preferably, R1, R2and R8are independently selected from -H, -CH3 (i.e. methyl) and -CH(CH3)2 (i.e. / sopropyl).

[0082] In one embodiment, R1, R2and R8may be independently selected from -H and a straight chain Ci-Ce-alkyl (e.g. methyl, ethyl, propyl, butyl, pentyl and hexyl). R1, R2and R8may be independently selected from -H and a straight chain Ci-Cs-alkyl (e.g. methyl, ethyl, propyl, butyl, pentyl). R1, R2and R8may be independently selected from -H and a straight chain Ci-C4-alkyl (e.g. methyl, ethyl, propyl, butyl). R1, R2and R8may be independently selected from -H and a straight chain Ci-Cs-alkyl (i.e. methyl, ethyl, propyl).

[0083] In one embodiment, R1, R2and R8may be independently selected from -H and a branched chain Ci-Ce-alkyl.

[0084] In one embodiment, the Ci-Ce-hydrocarbyl is an unsubstituted Ci-Ce-alkyl. Preferably, R1, R2and R8may be independently selected from -H and an unsubstituted Ci-Ce-alkyl, or from -H and an unsubstituted Ci-Cs-alkyl, or from -H and an unsubstituted Ci-C4-alkyl, or from - H and an unsubstituted Ci-Cs-alkyl.

[0085] In one embodiment, R1is -CH3. In another embodiment, R2is -H. In another embodiment, R8is -CH(CH3)2. In a preferred embodiment, R1is -CH3, R2is -H and R8is -CH(CH3)2.

[0086] R4, R6, R7, R10and R11may be independently selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl. The Ci-Ce-hydrocarbyl may include Ci-Ce-alkyl and Ci-Ce-alkenyl. Preferably, the Ci-Ce- hydrocarbyl may be a Ci-Ce-alkyl, optionally substituted with at least one group selected from -OH, halo, formyl or acetyl, or a Ci-Ce-alkenyl.

[0087] 17208777 CXB CXB In one embodiment, R4, R6, R7, R10and R11may be independently selected from -H and Ci- Ce-hydrocarbyl optionally substituted with one group selected from -OH, halo, formyl and acetyl. The Ci-Ce-hydrocarbyl may include Ci-Ce-alkyl and Ci-Ce-alkenyl. Preferably, the Ci-Ce-hydrocarbyl may be a Ci-Ce-alkyl, optionally substituted with one group selected from -OH, halo, formyl or acetyl, or a Ci-Ce-alkenyl.

[0088] In a preferred embodiment, the Ci-Ce-hydrocarbyl is a Ci-Ce-alkyl substituted with at least one -OH group. Ci-Ce-alkyl substituted with at least one -OH group includes the Ci-Ce-alkyl groups as described herein where at least one of the H atoms in the Ci-Ce-alkyl group is replaced with an -OH group. The Ci-Ce-alkyl group includes saturated straight or branched hydrocarbon radicals having from 1 to 6 carbon atoms.

[0089] In a preferred embodiment, the Ci-Ce-hydrocarbyl is a Ci-Ce-alkyl substituted with one -OH group.

[0090] R4, R6, R7, R10and R11may be independently selected from -H and Ci-Cs-alkyl substituted with at least one -OH group. Preferably, R4, R6, R7, R10and R11may be independently selected from -H and Ci-Cs-alkyl substituted with one -OH group. R4, R6, R7, R10and R11may be independently selected from -H and Ci-C4-alkyl substituted with at least one -OH group. Preferably, R4, R6, R7, R10and R11may be independently selected from -H and Ci- C4-alkyl substituted with one -OH group. R4, R6, R7, R10and R11may be independently selected from -H and Ci-Cs-alkyl substituted with at least one -OH group. Preferably, R4, R6, R7, R10and R11may be independently selected from -H and Ci-Cs-alkyl substituted with at least one -OH group. For example, R4, R6, R7, R10and R11may be independently selected from -H, -CH2OH, -CH(OH)CH3, -CH(CH2OH)CH3. Preferably, R4, R6, R7, R10and R11are independently selected from Ci-C2-alkyl substituted with one -OH group, for example, R4, R6, R7, R10and R11are independently selected from -CH2OH and - CH(OH)CH3.

[0091] In one embodiment, R6is -CH2OH. In another embodiment, R4, R7, R10and R11are - CH(OH)CH3. In a preferred embodiment, R6is -CH2OH and R4, R7, R10and R11are - CH(OH)CH3.

[0092] 17208777 CXB CXB R3may be to 3.

[0093] Preferably, n is selected from 0 to 2, or from 0 to 1 , more preferably n is 0.

[0094] In one embodiment, R3may be selected from

[0095] In a preferred embodiment, R12is -OH.

[0096] In a preferred embodiment, R3is (i.e. n is 0).

[0097] R5may be selected from or tautomers thereof, wherein m is selected from 1 to 5.

[0098] Preferably, m is selected from 1 to 4, or from 1 to 3, or from 2 to 4 or from 2 to 3. In a preferred embodiment, m is 3.

[0099] 17208777 CXB CXB In a preferred embodiment, R5is

[0100] \^N^R13

[0101] R9may be selected from0Hwhere R13is selected from -H and Ci-Ce-alkyl, and p is selected from 1 to 5.

[0102] Preferably, R13is selected from -H and Ci-Cs-alkyl. More preferably, R13is selected from -H and Ci-C2-alkyl. In a preferred embodiment, R13is -H.

[0103] Preferably, p is selected from 1 to 4, or from 1 to 3, or from 2 to 4, or from 2 to 3, or from 3 to 4. In a preferred embodiment, p is 3.

[0104] In one embodiment, R9is selected from:

[0105] In a preferred embodiment, R9is selected from or

[0106] In a further preferred embodiment,

[0107] 17208777 CXB CXB In one embodiment, n is selected from 0 to 2 and p is selected from 1 to 4. In a preferred embodiment, n is selected from 0 to 1 and p is selected from 3 to 4. In a further preferred embodiment, n is 0 and p is 3.

[0108] In one embodiment, n is selected from 0 to 2 and m is selected from 1 to 4. In a preferred embodiment, n is selected from 0 to 1 and m is selected from 2 to 3. In a further preferred embodiment, n is 0 and m is 3.

[0109] In one embodiment, m and p are selected from 1 to 3 and p is selected from 1 to 4. In a preferred embodiment, n is selected from 0 to 1 , m is selected from 2 to 3 and p is selected from 3 to 4. In a further preferred embodiment, n is 0, m is 3 and p is 3.

[0110] In one embodiment, n is selected from 0 to 2, m is selected from 1 to 3 and p is selected from 1 to 4. In a preferred embodiment, n is selected from 0 to 1 , m is selected from 2 to 3 and p is selected from 3 to 4. In a further preferred embodiment, n is 0, m is 3 and p is 3.

[0111] In a preferred embodiment, the compound of formula (I) is tautomers or salts thereof.

[0112] The compound of formula (I) may be a hexadentate iron chelator. The compound of formula (I) may have a high iron-binding affinity. Without wishing to be bound by a particular theory, iron chelation may be mediated by the hydroxamate groups of the N- hydroxy N-formyl ornithine and the N-hydroxy cyclo ornithine residues, along with the amide carboxyl and beta-hydroxy of the AHMPA moiety (i.e. 4-amino-3-hydroxy-2-methyl pentanoic acid). This strong iron-binding interaction may induce iron starvation in a wide range of pathogenic microbes resulting in growth inhibition.

[0113] The invention provides a composition comprising the compound of the first aspect, and optionally, an acceptable carrier or excipient (e.g. a pharmaceutically acceptable carrier).

[0114] 17208777 CXB CXB The composition may comprise the compound of formula (I) as described herein and optionally, an acceptable carrier or excipient (e.g. a pharmaceutically acceptable carrier). It is to be understood that the “composition” as described herein is intended to also encompass an “antifungal composition” and / or an “antibacterial composition” as referred to herein. Thus, all embodiments and examples described herein in the context of a “composition” apply mutatis mutandis to “antifungal composition” and an “antibacterial composition”. The antifungal composition as described herein is understood to refer to a composition of matter.

[0115] The antifungal composition (or the composition of matter) may comprise the compound of formula (I) in the salt form, or hydrate form. The compound of formula (I) may be in any isomeric form.

[0116] The expression “composition” as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. Such term in relation to the composition, is intended to encompass a product comprising the compound of formula (I), and optionally the additional ingredients that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the compositions of the present invention encompass any composition comprising the compound of formula (I) as described herein, and optionally an acceptable carrier or excipient.

[0117] By “acceptable” it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0118] The compositions (e.g. pharmaceutical compositions) or formulations are typically prepared by pharmaceutically acceptable carrier and, optionally, one or more optional ingredients. If necessary or desired, the resulting uniformly blended mixture can then be shaped or loaded into tablets, capsules, pills, canisters, cartridges, dispensers, and the like using conventional procedures and equipment.

[0119] 17208777 CXB CXB Preferably, the compound of formula (I) is used as an antimicrobial agent. In one embodiment, the compound of formula (I) is used as an antifungal agent and / or as an antibacterial agent. In one preferred embodiment, the compound of formula (I) is used as an antifungal agent. In an alternative preferred embodiment, the compound of formula (I) is used as an antibacterial agent. The compound of formula (I) may be delivered to a subject or a plant in the form of a composition as described herein.

[0120] The compound of formula (I) as described herein or composition as described herein may be used to treat or control a fungal disease or infection in a plant. The compound of formula (I) as described herein or composition as described herein may be suitable for use in therapy. The compound of formula (I) as described herein or composition as described herein may be suitable for use in treating a bacterial disease in a subject (i.e. animal or human). The compound of formula (I) as described herein or composition as described herein may be suitable for use as a medicament.

[0121] In the context of treating a subject, when intended for oral administration in a solid dosage form (i.e., as capsules, tablets, pills and the like), the composition (e.g. pharmaceutical compositions) will typically comprise a compound of formula (I) as the active ingredient.

[0122] The composition may comprise compound of formula (I) and no other ingredient. Alternatively, the pharmaceutical composition may comprise the compound (I) as the active ingredient and one or more pharmaceutically acceptable carriers. Suitable pharmaceutically acceptable carriers would be known by the person skilled in the art, for example, fats, water, physiological saline, alcohol (e.g., ethanol), glycerol, polyols, aqueous glucose solution, extending agent, disintegrating agent, binder, lubricant, wetting agent, stabilizer, emulsifier, dispersant, preservative, sweetener, colorant, seasoning agent or aromatizer, concentrating agent, diluent, buffer substance, solvent or solubilizing agent, chemical for achieving storage effect, salt for modifying osmotic pressure, coating agent or antioxidant, saccharides such as lactose or glucose; starch of corn, wheat or rice; fatty acids such as stearic acid; inorganic salts such as magnesium metasilicate aluminate or anhydrous calcium phosphate; synthetic polymers such as polyvinylpyrrolidone or polyalkylene glycol; alcohols such as stearyl alcohol or benzyl alcohol; synthetic cellulose derivatives such as methylcellulose, carboxymethylcellulose, ethylcellulose or hydroxypropylmethylcellulose; and other conventionally used additives such as gelatin, talc, plant oil and gum arabic.

[0123] 17208777 CXB CXB The composition (e.g. a pharmaceutical composition) comprising the compound of formula (I) can also be administered transdermally or transmucosally using known delivery systems and excipients. For example, the composition can be admixed with permeation enhancers such as propylene glycol, polyethylene glycol monolaurate, azacycloalkan-2-ones and the like, and incorporated into a patch or similar delivery system. Additional excipients including gelling agents, emulsifiers, and buffers, may also be used.

[0124] Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Aqueous solvents include, for example, distilled water for injection and / or physiological saline. Examples of non-aqueous solvents include alcohols such as ethanol.

[0125] The compositions (e.g. pharmaceutical compositions) may comprise one or more further active agents. This combination therapy involves using the compound of formula (I) combined with one or more of the further active agents, either formulated together (for example, packaged together in a single formulation) or formulated separately (for example, packaged as separate unit dosage forms).

[0126] Use as an antimicrobial agent to treat or control plant disease

[0127] The invention provides a use of the compound of formula (I) as described herein or the composition as described herein as an antimicrobial agent. The invention provides a use of the compound of formula (I) as described herein or the composition as described herein as an antifungal agent. The invention provides a use of the compound of formula (I) as described herein or the composition as described herein as an antibacterial agent.

[0128] The compound of formula (I) as described herein, or composition as described herein, may be used to treat a fungal or bacterial infection or disease. The fungal infection or disease and / or the bacterial infection or disease may be affecting plants.

[0129] Preferably, the antimicrobial agent is an antifungal agent. The compound of formula (I) as described herein has been found to exhibit antifungal properties. Therefore, the invention provides a use of a compound of formula (I) as described herein or composition as

[0130] 17208777 CXB CXB described herein as an antifungal agent. The invention also provides an antifungal use of a compound of formula (I) or composition as described herein.

[0131] Preferably, the compound of formula (I) as described herein or composition as described herein is effective against a filamentous fungus. Filamentous fungi include zygomycetes, basidiomycetes, and ascomycetes. Preferably, the filamentous fungus is of the family Mycosphaerellaceae. Preferably, the filamentous fungus is of the genus Zymoseptoria. More preferably, the filamentous fungus is Zymoseptoria tritici.

[0132] In a preferred embodiment, the compound of formula (I) as described herein or composition as described herein is effective against Zymoseptoria tritici.

[0133] Preferably, the compound of formula (I) as described herein or composition as described herein is effective against an oomycete or water mold. Preferably, the oomycete or water mold is of the family Peronosporaceae. Preferably, the oomycete or water mold is of the genus Phytophthora. More preferably, the oomycete or water mold is Phytophthora infestans.

[0134] In a preferred embodiment, the compound of formula (I) as described herein or composition as described herein is effective against Phytophthora infestans.

[0135] Compound of formula (I) may be used to treat diseases or infections caused by Venturia inaequalis, Microdochium nivale, Botrytis cinerea, Verticillium dahliae and / or Phytophthora cactorum. Compound of formula (I) may be used to treat scab (e.g. apple scab), Fusarium patch, mold (e.g. grey mold or botrytis bunch rot), verticillium wilt, seedling blight, ear blight and / or foot and root rot.

[0136] The antifungal agent may be used to treat a disease or infection of a plant. The plant may be a food crop including wheat, potato and tomato. Preferably, the plant to be treated is wheat, potato and tomato. Preferably, the plant to be treated is wheat or potato. In one embodiment, the plant to be treated is wheat. In one embodiment, the plant to be treated is potato.

[0137] Alternatively, preferably, the antimicrobial agent is an antibacterial agent. In addition to antifungal properties, compound of formula (I) as described herein has been found to

[0138] 17208777 CXB CXB exhibit antibacterial properties. Therefore, the invention provides a use of a compound of formula (I) as described herein or composition as described herein as an antibacterial agent. The invention also provides an antibacterial use of a compound of formula (I) or composition as described herein. The compound of formula (I) as described herein or the composition as described herein may be used to treat or control plant infections or diseases.

[0139] For example, plant infections or diseases caused by a bacterium include aster yellows, bacterial wilt, blight (e.g. fire blight and rice bacterial blight), canker, wildfire of tobacco, crown gall, rot (e.g. basal rot and soft rot) and scab. Thus, the compound of formula (I) as described herein or the composition as described herein may be used to treat or control bacterial infection or disease, such as aster yellows, bacterial wilt, blight (e.g. fire blight and rice bacterial blight), canker, wildfire of tobacco, crown gall, rot (e.g. basal rot and soft rot) and scab. Thus, the compound of formula (I) as described herein or the composition as described herein may be used for non-therapeutic applications. That is to say that the compound of formula (I) as described herein or the composition as described herein may not be used on human or animal subjects. The compound of formula (I) as described herein or the composition as described herein may be used for ex-vivo or in vitro applications.

[0140] Use as an antimicrobial agent for therapy in a subject

[0141] The invention provides the compound formula (I) as described herein or the composition as described herein for use in treating a bacterial disease or infection in a subject.

[0142] The invention provides the compound formula (I) as described herein or the composition as described herein for use in treating a fungal disease or infection in a subject.

[0143] In addition to antimicrobial properties of a compound of formula (I) for plant treatment, the compound of formula (I) also has antimicrobial properties against bacterial and fungal pathogens affecting (i.e. causing a disease or infection in) animal (especially human) subjects.

[0144] Therefore, the invention provides a compound of formula (I) as described herein, or a composition as described herein, for use in therapy. The invention provides a compound of

[0145] 17208777 CXB CXB formula (I) as described herein, or composition as described herein, for use as an antibacterial agent in a subject. The invention provides a compound of formula (I) as described herein, or a composition as described herein, for use in treating a bacterial disease in a subject. The invention provides a compound of formula (I) as described herein, or composition as described herein, for use as an antifungal agent in a subject. The invention provides a compound of formula (I) as described herein, or a composition as described herein, for use in treating a fungal disease in a subject.

[0146] The invention provides the compound of formula (I) as described herein for use as a medicament.

[0147] The invention also provides a method for treating a bacterial disease or infection comprising administering to a subject an effective amount of the compound of formula (I) as described herein or the composition as described herein.

[0148] The invention also provides a method for treating a fungal disease or infection comprising administering to a subject an effective amount of the compound of formula (I) as described herein or the composition as described herein.

[0149] The subject may be human or animal. Preferably, the subject is human.

[0150] The subject may suffer from a bacterial disease or infection. The subject may suffer from a fungal disease or infection. Alternatively, the subject may be immunocompromised. The subject may be suffering from a bacterial disease or infection and be immunocompromised. The subject may be suffering from a fungal disease or infection and be immunocompromised. Subjects with compromised immune systems include patients undergoing cancer therapy / treatment and transplant recipients (e.g. organ or bone marrow transplants). Immunocompromised subjects also include individuals suffering from chronic conditions such as HIV / AIDS or diabetes. The subject may also include hospitalized patients or patients with prolonged hospital stays, for example those who have undergone surgery, have an invasive device (e.g. catheters, some breathing devices etc) or are in intensive care units. The subject may also include individuals exposed to conflict and war zones (e.g. combat troops / soldiers) where hygiene, infrastructure and nutrition is poor.

[0151] 17208777 CXB CXB The bacterial disease or infection may be an opportunistic infection of the skin or soft tissue (e.g. wound infection), the urinary tract (e.g. kidneys, ureters or bladder), the lungs (e.g. pneumonia, bronchiolitis or tracheobronchitis), the blood (i.e. bacteremia) or the brain or spinal cord (e.g. meningitis).

[0152] The bacterial disease or infection may be selected from a wound infection, a urinary tract infection, pneumonia, meningitis, or bacteremia.

[0153] Preferably, the compound of formula (I) as described herein or composition as described herein is effective against gram-negative bacteria. More preferably, the gram-negative bacterium is of the family Moraxellaceae. More preferably, the gram-negative bacterium is Acinetobacter baumannii. The compound of formula (I) as described herein or composition as described herein may be effective against other gram-negative bacteria, e.g. Klebsiella pneumoniae. The compound of formula (I) as described herein or composition as described herein may also be effective against gram-positive bacteria, e.g. Staphylococcus aureus.

[0154] In a preferred embodiment, the compound of formula (I) as described herein or composition as described herein is effective against Acinetobacter baumannii.

[0155] The fungal disease or infection may be a disease of subcutaneous tissue, such as porotrichosis, chromoblastomycosis, and eumycetoma. The fungal disease or infection may be a disease of a systemic nature, for example, histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis, mucormycosis, aspergillosis, pneumocystis pneumonia and systemic candidiasis. The fungal disease or infection may be of superficial nature, for example, candidiasis or malassezia infections. The fungal disease or infection may be caused by a yeast, e.g. Cryptococcus neoformans.

[0156] The invention provides a method for treating a bacterial disease or infection in a subject (e.g. human), the method comprising applying an effective amount of the compound of formula (I) as described herein or the composition as described herein to the subject.

[0157] The invention provides a method for treating a fungal disease or infection in a subject (e.g. human), the method comprising applying an effective amount of the compound of formula (I) as described herein or the composition as described herein to the subject.

[0158] 17208777 CXB CXB The term “effective amount” as used herein means the amount of the compound of formula (I) as described herein or the composition as described herein that, when administered to a subject for treating a disease or infection, is sufficient to effect such treatment of the disease or infection. The “effective amount” will vary depending on the disease and its severity, and, if the subject is human or animal, the age and weight of the subject to be treated. The term “subject” includes, but is not limited to, animals such as, for example, mammals. Preferably, the subject is a human.

[0159] The invention provides a method for controlling a bacterial disease or infection in a subject (e.g. human), the method comprising applying an effective amount of the compound of formula (I) as described herein or the composition as described herein to the subject.

[0160] The invention provides a method for controlling a fungal disease or infection in a subject (e.g. human), the method comprising applying an effective amount of the compound of formula (I) as described herein or the composition as described herein to the subject.

[0161] The expression “control a disease” (or infection) is intended to encompass inhibition of the progression of the disease or infection and / or treatment of the disease or infection. That is to say that compound of formula (I) as described herein may stop the disease or infection from progressing or may reverse the effects of the disease or infection. The disease or infection may be an opportunistic disease or infection selected from a skin or soft tissue infection (e.g. wound infection), a urinary tract infection (e.g. kidneys, ureters or bladder), lung infection (e.g. pneumonia, bronchiolitis or tracheobronchitis), blood infection (i.e. bacteremia) or a brain or spinal cord infection (e.g. meningitis). The disease or infection may be a disease or infection caused by a bacterium of the Acinetobacter genus, such as Acinetobacter baumannii. Controlling a disease or infection (in addition to or alternatively to treatment) may be beneficial as it allows the patients to e.g. undergo surgeries or other treatments which weaken the immune system (e.g. chemotherapy) without leading to sepsis resulting from a bacterial or fungal infection.

[0162] The compound of formula (I) as described herein may be administered to a subject in the form of a pharmaceutical composition (e.g. the composition as described herein) or formulation. Such pharmaceutical compositions may be administered to the subject by any acceptable route of administration including, but not limited to, oral, topical (including transdermal) and parenteral modes of administration.

[0163] 17208777 CXB CXB The methods described herein may be in vitro methods or in vivo methods.

[0164] In the context of treating a subject, administration can be accomplished either by oral administration via tablets, pills, capsules, granules, powders, solutions, and the like, or parenteral administration, such as injections such as intra-articular, intravenous, and intramuscular injections, suppositories, ophthalmic solutions, eye ointments, or agents for external use, such as transdermal liquid preparations, ointments, transdermal patches, transmucosal liquid preparations, transmucosal patches, inhalers, and the like.

[0165] In oral administration, the daily dose is generally from about 0.0001 to 10 Omg / kg per body weight, administered in one portion or in 2 to 4 separate portions. The dose is appropriately decided upon in response to the individual case by taking the symptoms, the age, and the gender, and the like into consideration.

[0166] The compound of formula (I) may have an IC50 value against a bacterial pathogen, such as A. baumannii, of < 30 pM, < 25 pM, < 20pM, < 15pM, < 10 pM, < 5 pM, < 3 pM, or < 2 pM. The compound of formula (I) may have an IC50 value against a bacterial pathogen, such as A. baumannii, of < 35 pg / mL, < 30 pg / mL, < 25 pg / mL, < 20 pg / mL, <15 pg / mL, < 10 pg / mL, < 5 pg / mL, or < 3 pg / mL.

[0167] The compound of formula (I) may have a minimum inhibitory concentration (MIC) value against a bacterial pathogen, such as A. baumannii, of <125 pM, <120 pM, <110 pM, or <100 pM. The compound of formula (I) may have a minimum inhibitory concentration (MIC) value against a bacterial pathogen, such as A. baumannii, of <140 pg / mL, <130 pg / mL, or <128 pg / mL.

[0168] Use to treat or control plant disease

[0169] The invention provides a method for treating a plant to control a disease, the method comprises applying an effective amount of the compound as described herein or the composition as described herein to the plant, or a part of the plant.

[0170] 17208777 CXB CXB The invention also provides a method for treating a plant to control a disease, the method comprising applying an effective amount of the antibacterial composition as described herein to the plant, or a part of the plant.

[0171] The invention also provides a method for treating a plant to control a disease, the method comprising applying an effective amount of the antifungal composition as described herein to the plant, or a part of the plant.

[0172] The plant may be any plant suffering from a fungal disease such as a food crop. Preferably, the plant is selected from wheat, potato or tomato. More preferably, the plant is wheat. In a preferred alternative embodiment, the plant is potato or tomato.

[0173] The plant may be any plant suffering from a bacterial disease, such as aster yellows, bacterial wilt, blight (e.g. fire blight and rice bacterial blight), canker, wildfire of tobacco, crown gall, rot (e.g. basal rot and soft rot) or scab.

[0174] In the context of treating a plant, the fungal disease may be anthracnose, septoria leaf blotch, rust, wilt, blight, coils, scab, gall, canker, damping-off, root rot, mildew, dieback, common scab, early blight, fusarium dry rot, pink rot, potato virus Y, late blight, alternaria, black dot, black scurf and stem canker, gangrene, septoria leaf spot, leaf mold, or powdery mildew. The disease may be septoria leaf blotch. The disease may be late blight or potato blight. The bacterial disease may be aster yellows, bacterial wilt, blight (e.g. fire blight and rice bacterial blight), canker, wildfire of tobacco, crown gall, rot (e.g. basal rot and soft rot) or scab.

[0175] In a preferred embodiment, the plant is wheat, and the fungal disease is septoria leaf blotch.

[0176] In an alternative preferred embodiment, the plant is potato or tomato, and the fungal disease is late blight or potato blight. Preferably, the plant is potato, and the fungal disease is potato blight.

[0177] The compound of formula (I) may be administered to or applied to a plant in the form of a composition (as described herein) or formulation. Such compositions may be administered or applied to a plant by any acceptable route of administration including, but not limited to,

[0178] 17208777 CXB CXB spraying onto the plant or a part thereof, or addition to a water and / or nutrient solution provided to the plant.

[0179] The expression “control a disease” as used herein (in the context of methods and uses of the invention) is intended to encompass inhibition of the progression of the disease and / or treatment of the disease. That is to say that compound of formula (I) may stop the disease from progressing or may reverse the effects of the disease. The disease may be anthracnose, septoria leaf blotch, rust, wilt, blight, coils, scab, gall, canker, damping-off, root rot, mildew, dieback, common scab, early blight, fusarium dry rot, pink rot, potato virus

[0180] Y, late blight, alternaria, black dot, black scurf and stem canker, gangrene, septoria leaf spot, leaf mold, or powdery mildew. The disease may be septoria leaf blotch. The disease may be late blight or potato blight. The disease may be aster yellows, bacterial wilt, blight (e.g. fire blight and rice bacterial blight), canker, wildfire of tobacco, crown gall, rot (e.g. basal rot and soft rot) or scab. The disease or infection may be a disease or infection caused by a filamentous fungi of the family Mycosphaerellaceae, such as of the genus Zymoseptoria. For example, the disease or infection may be caused by Zymoseptoria tritici. The disease or infection may be caused by an oomycete or water mold of the family Peronosporaceae, such as of the genus Phytophthora. For example, the disease or infection may be caused by Phytophthora infestans. The disease or infection may be a disease or infection caused by Venturia inaequalis, Microdochium nivale, Botrytis cinerea, Verticillium dahliae and / or Phytophthora cactorum.

[0181] The term “effective amount” as used herein means the amount of the compound of formula (I) or the antifungal (or antibacterial) composition that, when administered to or applied to a plant for treating a disease, is sufficient to effect such treatment for the disease. The “effective amount” will vary depending on the disease and its severity, and / or, on the plant type, size and / or age.

[0182] The compound of formula (I) may have an IC50 value against a fungal pathogen, such as

[0183] Z. tritici or P. infestans, of < 5 pM, < 3 pM, < 2 pM , < 1 pM, or < 0.76 pM. The compound of formula (I) may have an IC50 value against a fungal pathogen, such as Z. tritici or P. infestans, of < 5 pg / mL, < 4 pg / mL, < 3 pg / mL, < 2.5 pg / mL, < 2 pg / mL, < 1.5 pg / mL, or < 1.0 pg / mL.

[0184] 17208777 CXB CXB The compound of formula (I) may have a minimum inhibitory concentration (MIC) value against a fungal pathogen, such as Z. tritici or P. infestans, of < 15 pM, < 13 pM, <10 pM, < 5 pM, or < 3 pM. The compound of formula (I) may have a minimum inhibitory concentration (MIC) value against a fungal pathogen, such as Z. tritici or P. infestans, of < 20 pg / mL, < 18 pg / mL, < 15 pg / mL, < 12 pg / mL, < 10 pg / mL, < 5 pg / mL, < 4 pg / mL, < 3 pg / mL, or < 2 pg / mL.

[0185] Biosynthetic Gene Cluster

[0186] The invention provides a method for producing a compound of formula (I) comprising synthesising the compound of formula (I) from a biosynthetic gene cluster encoding the peptides of SEQ ID NOs: 1-31 or peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31.

[0187] The invention provides the biosynthetic gene cluster encoding at least 3, at least 4, at least 5, at least 10, at least 15, at least 20, at least 25, or at least 28 peptides of any one of SEQ ID NOs: 1-31, or peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to at least 3, at least 4, least 5, at least 10, at least 15, at least 20, at least 25, or at least 28 peptides of SEQ ID NOs: 1-31. The invention also provides the biosynthetic gene cluster encoding the peptides of SEQ ID NOs: 1-31 , or sequences of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31.

[0188] The biosynthetic gene cluster may be used to produce the compound of formula (I).

[0189] The at least 3, at least 4, least 5, at least 10, at least 15, at least 20, at least 25, or at least 28 peptides of SEQ ID NOs: 1-31 may comprise peptides of SEQ ID NOs: 11 , 14, 15 and / or 16.

[0190] The invention provides a host cell comprising a plasmid encoding at least one of the peptides of SEQ ID NOs: 1-31. The host cell may comprise a plasmid encoding at least 2, at least 3, at least 4, at least 5, at least 10, at least 15, at least 20, at least 25, or at least 28 of the peptides of SEQ ID NOs: 1-31. The host cell may comprise a plasmid encoding all of the peptides of SEQ ID NOs: 1-31. The host cell may comprise two or three plasmids. Each plasmid may encode at least one of the peptides of any one of SEQ ID NO: 1-31. Each

[0191] 17208777 CXB CXB plasmid may encode at least 2, at least 3, at least 4, at least 5, at least 10, at least 15 of the peptides of any one of SEQ ID NOs: 1-31.

[0192] The plasmid may comprise a promoter. Each peptide expressed by the plasmid may be under control of a different promoter or the same promoter.

[0193] The invention also provides a method of producing a compound of formula (I) as described herein, the method comprises culturing the host cell as described herein under conditions suitable for the production of proteins. The method may comprise culturing the host cell under conditions suitable for the expression of peptides encoded by the biosynthetic gene cluster as described herein.

[0194] The invention provides the compound of formula (I) produced by the method as described herein.

[0195] SPECIFIC EMBODIMENTS (CLAUSES)

[0196] The invention will now be further described with reference to a list of specifically preferred embodiments, as set out in the following clauses.

[0197] 1. A compound of formula (I): wherein R1is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0198] R2is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0199] 17208777 CXB CXB wherein R12is selected from -H and -OH, and n is selected from 0 to 3;

[0200] R4is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0201] R5is or tautomers thereof, wherein m is selected from 1 to 5;

[0202] R6is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0203] R7is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0204] R8is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;

[0205] R9is selected from wherein R13is selected from -H and Ci-Ce-alkyl, and p is selected from 1 to 5;

[0206] R10is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;

[0207] R11is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl.

[0208] 17208777 CXB CXB 2. The compound of formula (I) according to clause 1 wherein R1, R2and R8are independently selected from -H, Ci-Ce-alkyl optionally substituted with at least one -OH group, and Ci-Ce-alkenyl.

[0209] 3. The compound of formula (I) according to any one of the preceding clauses wherein R1, R2and R8are independently selected from -H and Ci-Ce-alkyl optionally substituted with at least one -OH group.

[0210] 4. The compound of formula (I) according to any one of the preceding clauses wherein R1, R2and R8are independently selected from -H and a Ci-Ce-alkyl.

[0211] 5. The compound of formula (I) according to any one of the preceding clauses wherein R1, R2and R8are independently selected from -H and Ci-Cs-alkyl.

[0212] 6. The compound of formula (I) according to any one of the preceding clauses wherein R1is -CH3, R2is -H and R8is -CH(CH3)2.

[0213] 7. The compound of formula (I) according to any one of the preceding clauses wherein R4, R6, R7, R10and R11are independently selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl.

[0214] 8. The compound of formula (I) according to any one of the preceding clauses wherein R4, R6, R7, R10and R11are independently selected from -H, Ci-Ce-alkyl substituted with at least one -OH group, and Ci-Ce-alkenyl.

[0215] 9. The compound of formula (I) according to any one of the preceding clauses wherein R4, R6, R7, R10and R11are independently selected from -H and C1-C4 alkyl substituted with at least one -OH group.

[0216] 10. The compound of formula (I) according to any one of the preceding clauses wherein R4, R6, R7, R10and R11are independently selected from -CH(OH)CH3and -CH2OH.

[0217] 11 . The compound of formula (I) according to any one of the preceding clauses wherein R6is -CH2OH and / or R4, R7, R10and R11are -CH(OH)CH3.

[0218] 17208777 CXB CXB 12. The compound of formula (I) according to any one of the preceding clauses wherein R6is -CH2OH and R4, R7, R10and R11are -CH(OH)CH3.

[0219] 13. The compound of formula (I) according to any one of the preceding clauses wherein R3is selected from

[0220] 14. The compound of formula (I) according to any one of the preceding clauses wherein

[0221] 15. The compound of formula (I) according to any one of the preceding clauses wherein R12is -OH.

[0222] 16. The compound of formula (I) according to any one of the preceding clauses wherein n is selected from 0 to 1.

[0223] 17. The compound of formula (I) according to any one of the preceding clauses wherein n is 0, and p is 3.

[0224] 18. The compound of formula (I) according to any one of the preceding clauses wherein

[0225] 19. The compound of formula (I) according to any one of the preceding clauses wherein m is selected from 2 to 4.

[0226] 20. The compound of formula (I) according to any one of the preceding clauses wherein m is 3.

[0227] 17208777 CXB CXB 21 . The compound of formula (I) according to any one of the preceding clauses wherein r tautomers thereof.

[0228] 22. The compound of formula (I) according to any one of the preceding clauses wherein R13is selected from -H and Ci-Cs-alkyl.

[0229] 23. The compound of formula (I) according to any one of the preceding clauses wherein

[0230] R9is selected from

[0231] 24. The compound of formula (I) according to any one of the preceding clauses wherein

[0232] 25. The compound of formula (I) according to any one of the preceding clauses wherein p is selected from 3 to 4.

[0233] 26. The compound of formula (I) according to any one of the preceding clauses wherein

[0234] 17208777 CXB CXB 27. The compound of formula (I) according to any one of the preceding clauses wherein n is selected from 0 to 1 , m is selected from 2 to 3 and p is selected from 3 to 4.

[0235] 28. The compound of formula (I) according to any one of the preceding clauses wherein n is 0, m is 3 and p is 3.

[0236] 29. The compound of formula (I) according to any one of the preceding clauses wherein the compound of formula (I) is tautomers or salts thereof.

[0237] 30. A composition comprising the compound of formula (I) according to any one of the preceding clauses as an active ingredient and, optionally, an acceptable carrier or excipient.

[0238] 31. The composition according to clause 30, wherein the composition comprises formula (I) and no other ingredient.

[0239] 32. The composition according to clause 30, wherein the composition comprises formula (I) and one or more pharmaceutically acceptable carriers or excipients.

[0240] 33. A use of the compound of formula (I) according to any one of clauses 1-29, or the composition of any one of clauses 30-32, as an antimicrobial agent.

[0241] 34. The use according to clause 33, wherein the compound is effective against iron- scavenging microbes.

[0242] 35. The use according to clause 33 or 34 wherein the antimicrobial agent is as an antifungal agent.

[0243] 17208777 CXB CXB 36. The use according to clause 35, wherein the compound is effective against iron- scavenging fungi.

[0244] 37. The use according to clause 33 or 34 wherein the antimicrobial agent is an antibacterial agent.

[0245] 38. The use according to clause 37, wherein the compound is effective against iron- scavenging bacteria.

[0246] 39. The use according to any one of clauses 33 to 36 wherein the compound is effective against an oomycete or water mold, such as an oomycete of the family Peronosporaceae (e.g. Phytopthora infestans).

[0247] 40. The use according to any one of clauses 33 to 36, wherein the compound is effective against a filamentous fungus, such as a fungus of the family Mycosphaerellaceae (e.g. Zymoseptoria tritici).

[0248] 41. The compound of formula (I) according to any one of clauses 1-29, or the composition of clause 30, for use in treating a bacterial or fungal disease or infection in a subject.

[0249] 42. The compound of formula (I) or the composition for use according to clause 41 wherein the subject is human.

[0250] 43. The compound of formula (I) or the composition for use according to clause 41 or 42 wherein the subject is: a) suffering from a bacterial or fungal disease or infection; and / or b) immunocompromised.

[0251] 44. The compound of formula (I) or the composition for use according to any one of clauses 41 to 43, wherein the bacterial disease or infection is selected from a skin and soft tissue infection, such as a wound infection, a urinary tract infection, a lung infection, such as pneumonia, meningitis, or bacteremia.

[0252] 17208777 CXB CXB 45. The compound of formula (I) or the composition for use according to any one of clauses 41-44, wherein the compound of formula (I) is effective against gram-negative bacteria such as a bacterium of the family Moraxellaceae (e.g Acinetobacter baumannii).

[0253] 46. A method for treating a plant to control a disease, the method comprising applying an effective amount of the compound of formula (I) according to any one of clauses 1-29, or the composition of clause 30, to the plant, or a part of the plant.

[0254] 47. The method of clause 46, wherein the disease is selected from anthracnose, septoria leaf blotch, rust, wilt, blight, coils, scab, gall, canker, damping-off, root rot, mildew, dieback, common scab, early blight, fusarium dry rot, pink rot, potato virus Y, late blight, alternaria, black dot, black scurf and stem canker, gangrene, septoria leaf spot, leaf mold, or powdery mildew.

[0255] 48. The method of clause 47 wherein the disease is septoria leaf blotch or late blight or potato blight.

[0256] 49. The method of any one of clauses 46 to 48, wherein the plant is wheat, potato or tomato.

[0257] 50. The method of any one of clauses 46 to 49, wherein the plant is wheat.

[0258] 51. The method of clause 48 or 50, wherein the disease is septoria leaf blotch.

[0259] 52. The method of clause 46 to 49, wherein the plant is potato.

[0260] 53. The method of clause 46-49, wherein the plant is tomato.

[0261] 54. The method of clauses 48, 51 or 52, wherein the disease is late blight.

[0262] 55. A method for producing a compound of formula (I) according to any one of clauses 1-31 comprising synthesising the compound of formula (I) from a biosynthetic gene cluster encoding the peptides of SEQ ID NOs: 1-31, or peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31.

[0263] 17208777 CXB CXB 56. A biosynthetic gene cluster encoding at least 10 peptides of any one of SEQ ID NOs: 1-31, or at least 10 peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31.

[0264] These and other aspects of the invention will now be described with reference to the accompanying Figures, in which:

[0265] Figure 1A illustrates a dose response curve of compound of formula (I) (i.e. compound (I)) against A. baumannii from a luminescence-based assay.

[0266] Figure 1B illustrates a dose response curve of compound of formula (I) (i.e. compound (I)) against A. baumannii from an absorbance-based assay.

[0267] Figure 2A illustrates a dose response curve of compound of formula (I) (i.e. compound (I)) against Z. tritici from an absorbance-based assay.

[0268] Figure 2B illustrates a dose response curve of compound of formula (I) (i.e. compound (I)) against Z. tritici from a fluorescence-based assay.

[0269] Figure 3 illustrates a dose response curve of compound of formula (I) (i.e. compound (I)) against P. infestans from a resazurin-based assay against a positive control of Polymyxin B.

[0270] Figure 4 shows chromatograms obtained for compound of formula (I).

[0271] Figure 5 shows mass spectrum results for compound of formula (I).

[0272] Figure 6 shows1H NMR spectrum for compound of formula (I).

[0273] Figure 7 shows13C NMR spectrum for compound of formula (I).

[0274] Figure 8 shows a chemical structure of compound of formula (I) after characterization.

[0275] Figure 9 shows the architecture of the biosynthetic gene cluster.

[0276] 17208777 CXB CXB Figure 10 shows a map of the plasmid (PL00376) used to produce a compound of formula (I) according to Example 5.

[0277] Figure 11 provides cloning confirmation of a compound of formula (I) using PCR.

[0278] Figure 12a shows LC-MS trace for [M-2H+Fe(l 11)]+ion peak for a compound of formula (I) obtained according to Example 5 compared to the LC-MS trace obtained from a nonengineered strain control.

[0279] Figure 12b shows LC-MS trace for [M+2H]2+ion peak for a compound of formula (I) obtained according to Example 5 compared to the LC-MS trace obtained from a nonengineered strain control.

[0280] Figure 12c shows LC-MS trace for [M-2H+ Fe(l 11)+ H]2+ion peak for a compound of formula (I) obtained according to Example 5 compared to the LC-MS trace obtained from a nonengineered strain control.

[0281] Figure 13 shows chromatograms and UV spectra at different wavelengths obtained after purification of a compound of formula (I) according to Example 6. In particular, this figure shows the Total Ion Chromatogram (TIC), Base Peak Chromatogram (BPC), UV at 210 nm, UV at 254 nm, UV at 280 nm and UV at 300 nm for purified compound (I).

[0282] Figure 14 shows the effect of treatment with Compound (I) at different concentrations on disease caused by Zymoseptoria tritici on winter wheat plants. Compound (I) was added 24 hours prior to inoculation, with disease severity assessed 22 days later. Percent disease control is normalised to disease severity in water control. Bars represent standard error of mean.

[0283] Figure 15 provides a visual representation of the different levels of disease severity for wheat Zymoseptoria tritici based on the percentage of leaf area affected. Six examples of wheat leaves are provided with disease severities ranging from 1 % to 75% (areas of disease are represented in black).

[0284] Figure 16 illustrates response curves for compound (I) and four different positive controls against four agricultural pathogens from an absorbance-based assay. Fig. 16a is a dose

[0285] 17208777 CXB CXB response curve for compound (I) against Microdochium nivale. Fig 16b is a dose response curve for compound (I) against Phytophthora cactorum. Fig 16c is a dose response curve for compound (I) against Verticillium dahlia. Fig 16d is a dose response curve for compound (I) against Venturia inaequalis. Fig. 16e shows a dose response curve for positive control prothioconazole-desthio (pro des) against Microdochium nivale. Fig. 16f shows a dose response curve for positive control mandipropamid (mandi) against Phytophthora cactorum. Fig 16g shows a dose response curve for azoxystrobin (azoxy) against Verticillium dahlia. Fig.16h shows a dose response curve for fluxapyroxad (flux) against Venturia inaequalis.

[0286] Figure 17 illustrates response curves for compound (I) and two different positive controls against different strains of Zymoseptoria tritici from an absorbance-based assay. Fig. 17a is a dose response curve for compound (I) against a susceptible strain of Zymoseptoria tritici. Fig 17b is a dose response curve for compound (I) against a resistant strain of Zymoseptoria tritici, Haplotype H4 with reduced sensitivity to azoles. Fig 17c is a dose response curve for compound (I) against a succinate dehydrogenase inhibitor (SDHI) resistant strain of Zymoseptoria tritici. Fig 17d shows a dose response curve for positive control fluxapyroxad (flux) against a susceptible strain of Zymoseptoria tritici. Fig 17e shows a dose response curve for positive control prothioconazole-desthio (pro des) against a resistant strain of Zymoseptoria tritici, Haplotype H4 with reduced sensitivity to azoles. Fig. 17f shows a dose response curve for positive control fluxapyroxad (flux) against a succinate dehydrogenase inhibitor (SDHI) resistant strain of Zymoseptoria tritici.

[0287] Figure 18 shows the ratio of control as a function of the concentration Compound (I), and two control compounds: carbonyl cyanide 3-chlorophenylhydrazone, and chlorpromazine to evaluate cellular toxicity. The dashed lines represent the significant cut-off from vehicle control and was used to calculate the MEC (minimum effective concentration). The filled diamonds represent the mean data points for each concentration plus or minus standard deviation. The solid lines at the top of the graph represent historical maximum responses which were used to calculate AC50. The historical minimum, also used to calculate AC50, is represented by the x-axis.

[0288] Figure 19 shows the ratio of control as a function of the concentration of a) Compound (I) in media containing glucose, b) Compound (I) in media containing galactose, c) rotenone (control compound) in media containing glucose, d) rotenone (control compound) in media

[0289] 17208777 CXB CXB containing galactose, e) chlorpromazine (control compound) in media containing glucose, f) chlorpromazine (control compound) in media containing galactose to evaluate mitochondrial toxicity. The dashed lines represent the significant cut-off from vehicle control and was used to calculate the MEC (minimum effective concentration). The filled diamonds represent the mean data points for each concentration plus or minus standard deviation. The solid lines represent historical maximum which were used to calculate AC50. The historical minimum, also used to calculate AC50, is represented by the x-axis.

[0290] EXAMPLES

[0291] The following non-limiting examples further illustrate the present invention.

[0292] Example 1 - Bacterial Growth Assay

[0293] 1.1 - Acinetobacter baumannii

[0294] A. baumannii (RS-AA52) was generated by transforming A. baumannii ATCC17978, obtained from DSMZ Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (catalogue number: DSM 105126), with luminescence marker pUT mini-Tn5 luxON (RS-AA52). A. baumannii RS-AA52 was stored in 30% glycerol at -80 °C. To revive the bacteria, a loop of the frozen glycerol stock (obtained from Fisher Scientific (catalogue number: 11433297)) was spread onto Mueller-Hinton agar plates containing 50 pg / mL of kanamycin (kan50obtained from Fisher Scientific (catalogue number: 10031553)) and incubated at 37 °C overnight. Plates not immediately used for bioassays were stored at 4 °C for up to 7 days. For starter cultures, 2 mL Cation-Adjusted Mueller-Hinton Broth (CA- MHB - obtained from Sigma-Aldrich (catalogue number: 90922-500G)) with kan50were dispensed into a 14 mL culture tube and inoculated with a colony of A. baumannii. Tubes were incubated at 37 °C, with shaking at 300 rpm overnight.

[0295] For bioassays 12.5 pL of samples or the following controls were added to a sterile 384-well microtitre plate in triplicate. Final concentrations were: 0.25% DMSO (negative control); 15 pg / mL amikacin (positive antibiotic control, obtained from Amikacin - Fisher Scientific (catalogue number: 15589343)); uninoculated CA-MHB (sterility control, obtained from Sigma-Aldrich (catalogue number:90922-500G)); 1.25 ug / mL Meropenem (antibiotic quality

[0296] 17208777 CXB CXB control, inhibiting at <100%, obtained from Fisher Scientific (catalogue number:16481957)). The A. baumannii bioassay inoculum was prepared when the optical density (ODeoo) of each starter culture reached 5.5 - 6.5. The ODeoo was adjusted to 0.01 in 15 mL CA-MHB per assay plate. The UK Robotics D2 robot was used to dispense 37.5 pL of pathogen suspension into the appropriate experimental and control wells of a sterile 384-well bioassay plate. The plate was sealed with a breathable membrane, the baseline time 0 (to) measurements of ODeoo and luminescence (250 ms integration time) were recorded, and the plate was incubated at 37 °C while shaking at 300 rpm. At 4- and 22-h timepoints, luminescence and ODeoo were measured using a TECAN Spark® Multimode Microplate Reader.

[0297] 1.1.1 - Bioassay Data analysis

[0298] A. baumannii

[0299] Percentage inhibition of each sample was calculated against A. baumannii as follows:

[0300] 1. Each sample was time normalised to to: OD600(t0norm) = OZ)600(t4) - OD600(t0

[0301] 2. The mean ± standard deviation of the three independent replicates was calculated.

[0302] The mean of the negative control samples was used as control for full growth.

[0303] Therefore, the percentage inhibition of each sample was calculated using the following formula:

[0304] The percentage inhibition was calculated separately for ODeoo and luminescence.

[0305] Figure 1A shows a dose response curve of compound (I) against A. baumannii from a luminescence-based assay. IC50 values are derivable from these results. Particularly, an IC50 of 23.2 pM was derived from these results which indicates the concentration of compound (I) required to inhibit 50% of the monitored biological process in the A. baumannii strain. The minimum concentration of compound (I) required to inhibit the metabolic activity to a suitable extent is 100 pM. A suitable extent of inhibition is represented by the point at which the dose response curve plateaus.

[0306] 17208777 CXB CXB Figure 1B shows a dose response curve of compound (I) against A baumannii from an absorbance-based assay. IC50 values are derivable from these results. Particularly, an IC50 of 1.62 pM was derived from these results which indicates the concentration of compound (I) required to inhibit 50% of the monitored biological process in the A. baumannii strain. The minimum concentration of compound (I) required to inhibit the metabolic activity to a suitable extent is 100 pM. A suitable extent of inhibition is represented by the point at which the dose response curve plateaus. The difference in the IC50 results derived from the absorbance and luminescence (fluorescence) assays is due to the detection mechanism where the absorbance assay typically measures the optical density of a solution and the luminescence (fluorescence) assay measures light emission from a chemical reaction.

[0307] 1.2 - Bioactivity Data

[0308] MIC and IC50 Calculations

[0309] The minimum inhibitory concentration (MIC) was defined as the minimum concentration of a compound of formula (I) required to inhibit the metabolic activity of a bacterial or fungal pathogen to a suitable extent, such as by 50 or 75%. The half maximal inhibitory concentration (IC50) was calculated in R using the ‘drm’ function from the ‘drc’ package (version 3.0.1). The values were determined using a four-parameter logistic model.

[0310] Table 1 - MIC and IC50 Calculations for bacterial pathogens

[0311] Example 2 - Fungal Growth Assay

[0312] 2.1 - Zymoseptoria tritici

[0313] The fluorescent Z. tritici strain (RS-AA10) (CABI genetic resource collection), (catalogue number: IMI 505230) was generated by transforming Z. tritici IPO323 with plasmid

[0314] 17208777 CXB CXB pBACTO4 (eAA69), which carries the ZTGFP_StrongKozak insert in a pCAMBIA0380 backbone. To create the bioassay inoculum, Z. tritici RS-AA10 was streaked out from glycerol stocks onto YMS agar plates containing 1 pL / mL of a 40 mg / mL carboxin stock solution. The plate was incubated in the dark at 18 °C for 1-2 weeks. Once colonies were visible, they were used to inoculate 10 mL of 25% YMS broth, which was incubated at 18 °C while shaking at 200 rpm for 3 days. 100 pL of this starter culture was transferred into fresh 25% YMS media, and incubated for another 24 h. Prior to the assay, the inoculum was adjusted to an ODeoo of 0.1 .

[0315] For bioassays 12.5 pL of samples or the following controls were added to a sterile 384-well microtitre plate in triplicate at final concentrations of: 0.25% DMSO (negative control, obtained from Fisher Scientific (catalogue number: 10103483)); 15 pg / mL amphotericin B (positive antifungal control, obtained from Fisher Scientific (catalogue number: 15333671)); uninoculated 25% YMS media (sterility control). Each test well was filled with 37.5 pL of the fungal inoculum. After inoculation, the plate was incubated in the dark at 18 °C for 48 h. ODeoo and green fluorescence (excitation 485 nm, emission 535 nm) were measured at two time points (to (i.e. at the start of incubation) and Ue (i.e. after 48 hours from incubation) using a TECAN Spark® Multimode Microplate Reader.

[0316] YMS media composition: Yeast extract - Fisher Scientific (catalogue number: 10225203), Bacto Malt extract - Fisher Scientific (catalogue number: 16289841), Sucrose - Thermo Scientific (catalogue number: A15583.0E).

[0317] 2.1.2 - Bioassay Data analysis

[0318] Percentage inhibition of each sample was calculated against Z. tritici as follows:

[0319] 1. Each sample was time normalised to to: OD600(t0norm) = OD600t48- OD600(t0

[0320] 2. The mean ± standard deviation of the three independent replicates was calculated.

[0321] The mean of the negative control samples was used as control for full growth.

[0322] Therefore, the percentage inhibition of each sample was calculated using the following formula:

[0323] 17208777 CXB CXB The percentage inhibition was calculated separately for ODeoo and fluorescence.

[0324] Figure 2A illustrates a dose response curve of compound (I) against Z. tritici from an absorbance-based assay. IC50 values are derivable from these results. In particular, an IC50 of 0.63 pM was derived from these results which indicates the concentration of compound (I) required to inhibit 50% of the monitored biological process in the Z. tritici strain. The minimum concentration of compound (I) required to inhibit the metabolic activity to a suitable extent is 3.13 pM. A suitable extent of inhibition is represented by the point at which the dose response curve plateaus.

[0325] Figure 2B illustrates a dose response curve of compound (I) against Z. tritici from a fluorescence-based assay. IC50 values are derivable from these results. In particular, an IC50 of 0.76 pM was derived from these results which indicates the concentration of compound (I) required to inhibit 50% of the monitored biological process in the Z. tritici strain. The minimum concentration of compound (I) required to inhibit the metabolic activity to a suitable extent is 1.56 pM. A suitable extent of inhibition is represented by the point at which the dose response curve plateaus. The difference in the IC50 results derived from the absorbance and fluorescence assays is due to the detection mechanism where the absorbance assay typically measures the optical density of a solution and the luminescence (fluorescence) assay measures light emission from a chemical reaction.

[0326] 2.2 - Phytophthora inf estans

[0327] P. infestans strain FAB_22012A 6AI (RS-AA24) was obtained from the UK’s Crop Health & Protection agency (catalogue number: FAB_22012A 6AI) and is continuously grown on Rye B Agar plates. Sporangia for bioassay inoculation were harvested from 2-3 weeks old plates. To create the inoculum, a mature plate was flooded with 50 mL of ice-cold water, the mycelia were physically manipulated to detach the sporangia which were filtered through a 60 pm mesh. Sporangia were manually counted and stored at 4 °C for 24 h. This aids in the release of zoospores from the sporangia. Filled and empty sporangia were then counted resulting in a ration of filled and empty sporangia. The sporangia suspension was centrifuged at 1000 rpm for 10 min, the supernatant discarded, and the cells were resuspended in sufficient amounts of Plich media to create a sporangia concentration of 1.5 x 105sporangia / mL.

[0328] 17208777 CXB CXB For bioassays 12.5 pL of samples of the following controls were added to a sterile 384-well microtitre plate in triplicate, at final concentrations of: 0.25% DMSO (final concentration, negative control); 15 pg / mL cycloheximide (positive fungicide control, obtained from Fisher Scientific (10661185)); Plich media (sterility control). Each test well was filled with 37.5 pL of the P. infestans sporangia inoculum. After inoculation the plate was incubated in the dark at 18 °C for 72 h. Following incubation, 5 pL of a 0.015% Resazurin stock solution (obtained from Thermo Scientific, catalogue number: 189900010) was added to each well and fluorescence (excitation 535 nm, emission 595 nm) measurements were recorded as relative fluorescence units (RFUs) at two time points to (i.e. immediately after adding Resazurin to the wells) and t4 (i.e. after 4 hours of incubation with Resazurin) using a TECAN Spark® Multimode Microplate Reader.

[0329] Plich Media composition: Glucose - Thermo Scientific (catalogue number: 170080025), Sucrose - Thermo Scientific (catalogue number: A15583.0E), L-Asparagine - Thermo Scientific (catalogue number: 371601000), Potassium Phosphate Monobasic- Fisher Scientific (catalogue number: 10458153), Magnesium sulfate heptahydrate - Thermo Scientific (catalogue number: 447165000), Cholesterol - Thermo Scientific (catalogue number: A11470.18), Ascorbic Acid - Thermo Scientific (catalogue number: 105021000), Thiamine hydrochloride - Thermo Scientific (catalogue number: 148991000), Zinc sulfate heptahydrate - Thermo Scientific (catalogue number: A12915.36), Iron(ll) sulfate heptahydrate - Thermo Scientific (catalogue number: A15178.36), Manganese(ll) chloride tetrahydrate - Fisher Scientific (catalogue number: 15693390)

[0330] 2.2.2 - Bioassay Data analysis

[0331] Percentage inhibition of each sample was calculated against P. infestans as follows:

[0332] 1. Each sample is time normalised to to: RFU(t0norm) = RFU(t^ - RFU(t0)

[0333] 2. The mean ± standard deviation of the three independent replicates is calculated. The mean of the negative control samples is used as control for full growth.

[0334] Therefore, the percentage inhibition of each sample is calculated using the following formula:

[0335] 17208777 CXB CXB Figure 3 illustrates a dose response curve of compound (I) against P. infestans from a resazurin-based assay, in comparison to the polymyxin B control. In this assay a Resazurin dye (obtained from Thermo Scientific, catalogue number: 189900010) was used as an indicator for the presence of metabolic activity of P. infestans. According to our data metabolic activity was inhibited at a concentration of 12.5 pM, plus an IC50 of 1.94 pM was derived from these results which indicates the concentration of compound (I) required to inhibit 50% of the monitored biological process in the P. infestans strain. The minimum concentration of compound (I) required to inhibit the metabolic activity to a suitable extent is 12.5 pM. A suitable extent of inhibition is represented by the point at which the dose response curve plateaus. Polymyxin B (PmB), which had an IC50 of 1.19 pM in this assay, was used as a control to compare the results of compound (I) to an active compound. Polymyxin B was obtained from Sigma-Aldrich (catalogue number: P4932-1MU). The results show that compound (I) is in good agreement in terms of inhibitory activity with positive control Polymyxin B.

[0336] 2.3 - Bioactivity Data

[0337] MIC and IC50 calculations

[0338] The minimum inhibitory concentration (MIC) was defined as the minimum concentration of a compound of formula (I) required to inhibit the metabolic activity of a bacterial or fungal pathogen to a suitable extent (here about 77%). The half maximal inhibitory concentration (IC50) was calculated using R software.

[0339] Table 2 - MIC and IC50 Calculations for fungal and fungal-like pathogens

[0340] ND - not determined

[0341] Example 3- Production of compound of formula (I)

[0342] 17208777 CXB CXB 3.1 - Construct outline

[0343] Compound of formula (I) (specifically compound (I)) was produced via a plasmid-borne biosynthetic gene cluster, maintained in the heterologous production host Pseudomonas putida (strain DSM 6125), using an antibiotic selection marker (aminoglycoside phosphotransferase, conferring resistance to Kanamycin). Additionally, a secondary, supplementary plasmid was maintained within the host via an orthogonal antibiotic selection marker (chloramphenicol acetyltransferase, conferring resistance to Chloramphenicol). A PPTase enzyme, dedicated exporter protein, and chemical precursor required for the synthesis of Compound of formula (I) (specifically compound (I)) was synthesized via the host supplementary plasmid.

[0344] The architecture of the biosynthetic gene cluster is shown in Figure 9.

[0345] The sequence of proteins expressed by the biosynthetic gene cluster, their function and DNA size are shown in Table 3 below.

[0346] Table 3- The sequence, function and DNA size of proteins expressed by the biosynthetic gene cluster

[0347] 17208777 CXB CXB

[0348] 17208777CXBCXB

[0349] 17208777CXBCXB

[0350] 17208777CXBCXB

[0351] 17208777CXBCXB

[0352] 17208777CXBCXB

[0353] 17208777CXBCXB

[0354] 17208777CXBCXB

[0355] 17208777CXBCXB

[0356] 17208777CXBCXB

[0357] 17208777CXBCXB

[0358] 17208777CXBCXB

[0359] 17208777CXBCXB

[0360] 17208777CXBCXB

[0361] 17208777CXBCXB

[0362] 17208777CXBCXB

[0363] 3.2 - Heterologous expression of compound of formula (I) A swab of the glycerol stock consisting of the heterologous host containing both the supplementary plasmid and the biosynthetic gene cluster of compound (l)-containing plasmid, was streaked out onto LB agar and incubated at 30°C for 16 hours. The agar plate contained both relevant antibiotics, at 50 pg / mL Kanamycin and 25 pg / mL Chloramphenicol, selecting for the maintenance of both plasmids. A single colony was picked from the plate post-incubation for inoculation of a 5 mL LB broth pre-culture, also containing both antibiotics at 50 pg / mL Kanamycin and 25 pg / mL Chloramphenicol. This

[0364] 17208777 CXB CXB culture was incubated for 16 hours at 30°C, shaking at 200 rpm. The pre-culture was used to inoculate a secondary pre-culture of 50 mL LB broth in a 250 mL baffled erlenmeyer flask (with 50 pg / mL Kanamycin and 25 pg / mL Chloramphenicol) with a 2% inoculum (1 mL) and was incubated for 16 hours at 30°C, shaking at 125 rpm.

[0365] Production cultures of compound (I) were produced across two baffled 2 L erlenmeyer flasks containing 500 mL M9 minimal media (0.1 mM CaCh, 1 mM MgSCL, 3 g / L KH2 O4, 0.5 g / L NaCI, 6.78 g / L Na2HPO4, 1 g / L NH4CI, 1% Glycerol, 50 pg / mL Kanamycin and 25 pg / mL Chloramphenicol) - for a total production culture volume of 1 L across the 2 flasks. The 50 mL pre-culture was used to inoculate the M9 media with a 2% inoculum (10 mL preculture added to each flask). Production cultures were incubated at 30°C, shaking at 125 rpm, for 16 hours at which point 1 mM IPTG was added to induce the expression of genes on the supplementary plasmid. Thereafter, the production cultures were incubated for a further 7 days at 30°C, shaking at 125 rpm, prior to harvesting and extraction.

[0366] Example 4 - Chemical Characterization

[0367] Compound of formula (I) produced as in Example 3 was analysed structurally.

[0368] 4.1 - Liquid Chromatography Mass Spectrometry (LCMS)

[0369] LC-MS data was collected on an Agilent 1290 Infinity II UHPLC coupled to an Agilent 6546 quadrupole time-of-flight (Q-TOF) mass spectrometer. Samples were prepared in H2O + 0.1 % formic acid, at a crude concentration of < 5 mg / mL in 2 mL vials or 96-well plates. Visible precipitate was removed via filtration or centrifugation as required. For data collection, 2 pL of each sample of interest was injected on to a Luna Omega 3.0 pm Polar C18 column (50 x 2.1 mm, 100 A, Phenomenex), eluting with a linear gradient of 0 to 98 % acetonitrile (ACN) over 6 min, with untargeted MS1 and MS2 positive mode data collected throughout.

[0370] 4.1.1 - Multisampler Settings

[0371] The multi-wash setting was enabled with 3 needle washing steps performed in sequence for 5 s each with isopropanol (IPA), Magic mix (IPA:ACN:methanol(MeOH):H2O 1 :1 :1 :1 + 0.2 % formic acid) and H2O. Needle height position was set to 3 mm with vial bottom sensing enabled.

[0372] 4.1.2 - Liquid Chromatography

[0373] 17208777 CXB CXB Line A was H2O with 0.1 % formic Acid, Line B was ACN with 0.1 % formic acid. Solvent flow rate was 0.45 mL / min and column oven temperature 40 °C. Gradient was 0 % B 0.0 - 1.0 min, 0 - 98 % B 1.0 - 7.0 min, 98 % B 7.0 - 8.0 min, with 1.0 min of post-time for equilibration at 0% B.

[0374] 4.1.3 - Electrospray Ionisation Source Settings

[0375] All data was collected in positive ion mode. Gas temperature = 325 °C, gas flow = 11 (L / min), nebuliser = 50 (psig), sheath gas temperature = 325 °C, sheath gas flow = 12, capillary voltage = 4 kV, fragmentor voltage = 125 V, skimmer = 65, octopole RF = 650.

[0376] 4.1.4 - MS1 Data Collection

[0377] Data was collected in the range 100 - 1700 m / z with a scan rate of 4 spectra / s. Data storage threshold was set to 1000. The internal reference ions (121.05087 and 922.0098 m / z) are permanently infused to maintain mass accuracy throughout data collection.

[0378] 4.1.5 - MS2 Data Collection

[0379] Data was collected in a data dependent manner using a top 3 method in the range 50 - 1700 m / z with a scan rate of 8 spectra / s. Data storage threshold was set to 50. The PC was enabled for precursor selection with a minimum of height of 10,000 required to trigger fragmentation, precursors were sorted by abundance only. The system calibrant ions (121.05087 and 922.0098 m / z) were excluded from selection with a ppm error of 20. Precursors were isolated with a narrow isolation width (~1.3 amu). Collision energy for fragmentation was set using a formula of slope 3 with and offset of 10 V. Active exclusion was enabled with exclusion activated after collecting 1 spectrum and exclusion was released again after 0.05 min (3 s).

[0380] 4.1.6 - UV Data Collection

[0381] UV data was collected at wavelengths of 210, 254, 280 and 300 nm with a bandwidth of 4 nm.

[0382] 4.1.7 - Results

[0383] Figure 4 shows the retention time and purity of the isolated compound of formula (I) when Fe-bound. Purity was determined by m / z profile (total ion chromatogram, base peak chromatogram as well as UV profile at 210 and 254 nm). The EIC chromatogram shows the presence of the targeted ion of 1334.5405 m / z.

[0384] 17208777 CXB CXB Figure 5 shows mass spectrum results for the peak of interest. The mass profile shows the experimental [M-2H+Fe(l 11)]+and [M-2H+Fe(lll)+H]2+ions for compound of formula (I), in agreement with predicted values. The mass profile data for the experimental ions is listed in the table below. The results show good experimental agreement between the proposed structure and the theoretical masses.

[0385] The mass spectra results are summarised in Table 4 below.

[0386] Table 4 - Mass Spectra data

[0387] The compound of formula (I) was found to have the following properties:

[0388] Table 5 - compound of formula (I) properties

[0389] 4.2- Nuclear Magnetic Resonance (NMR)

[0390] Structural characterisation is carried out by acquisition of one dimensional (1 D) and two dimensional (2D) NMR data and full assignment for elucidation. Chemical shifts are determined by1H and13C (800 MHz and 201 MHz) NMR spectroscopy using a Bruker 800 MHz instrument. Data analysis and peak assignment is performed using MestreNova software.

[0391] 4.2.1 - Sample Preparation

[0392] Samples were dissolved in 0.560 pL of the deuterated solvent of choice based on solubility testing. If needed, the sample was sonicated for a few minutes then transferred into a 5 mm NMR tube.

[0393] 17208777 CXB CXB 4.2.2 - Preliminary1H data Acquisition

[0394] The NMR tubes containing the samples were placed in the autosampler and a preliminary1H data was acquired (ns = 1 , relaxation delay = 1 sec). Spectral width should be minimum from 14 to -2 ppm. Spectra were recorded at room temperature and chemical shifts were referenced to the solvent signal. The1H spectrum was inspected for concentration and purity to determine if quality and concentration were sufficient for further analysis.

[0395] 4.2.3 -13C data Acquisition

[0396] The minimum spectral width was 230 to -10 ppm, relaxation delay > 2 s. Number of scans was determined based on sample concentration, typically a minimum of 500 up to 4000 scans are required.

[0397] 4.2.4 - Secondary NMR Data Acquisition

[0398] Homonuclear correlations (1H-1H) were determined based on COSY, NOESY and ROESY experiments, (1H-13C) hetero-correlations were determined based on HMQC and HMBC experiments. A NOAH supersequence (BQCR or BOON) was used with 8 - 16 scans, with the acquisition spectral width the same as for 1 D data.

[0399] 4.2.5 - Results

[0400] Figure 6 shows the1H NMR spectrum for compound of formula (I).

[0401] Figure 7 shows the13C NMR spectrum for compound of formula (I).

[0402] The NMR peak data obtained, and their respective assignments are set out in Table 6 below.

[0403] Table 6- NMR Peak Assignments

[0404] 17208777 CXB CXB

[0405] 17208777CXBCXB

[0406] 17208777CXBCXB interchangeable

[0407] 17208777 CXBCXB Figure 8 shows the chemical structure of compound of formula (I) after characterisation.

[0408] Example 5 - Production of compound of formula (I) with heterologous expression strain - RS-AI48

[0409] 5.1 - Construct outline

[0410] P. putida DSM 6125 was transformed with plasmid PL00375 to yield the heterologous expression host. PL00375 harbours several genes which contribute to the successful activation of heterologously expressed BGCs, provide key precursors in compound synthesis, and facilitate extracellular transport of resulting compounds. To enable successful heterologous expression, multiple enzymes were inserted into a parent plasmid containing pBBR1 replication origin and apramycin resistance marker to generate PL00375. These include, a promiscuous phosphopantotheinyl transferase from Bacillus subtilis (sfp gene), enzymes for methyl malonyl coA production (pccB and accA2 from Streptomyces coelicolor A3) and a mutated enterobactin siderophore transporter (FepA L8T from Escherichia coli). No modifications were made to the DSM 6125 genomic background.

[0411] A further plasmid, (+PL00376; SEQ ID NO: 32) was provided with the biosynthetic gene cluster encoding the amino acid sequences as set out in Table 3 above. Figure 10 shows a map of this heterologous expression plasmid. The plasmid contains 92,540 base pairs. The map illustrates the replication of origin DNA sequence (oriV), which serves as the starting point for DNA replication; the trfA gene, which encodes the replication initiator protein and KanR, which acts as an antibiotic resistance marker along with the biosynthetic gene cluster encoding sequences as set out in Table 3. P. putida DSM 6125 (+PL00375) heterologous expression host was further transformed with +PL00376 to yield the heterologous expression strain RS-AI48.

[0412] 5.2 - Heterologous Expression of compound of formula (I)

[0413] Strain RS-AI48 was streaked out onto LB (Lennox) agar plates containing 50 pg / mL Kanamycin and 50 pg / mL Apramycin and incubated in a standing incubator at 30°C overnight. A single colony was used to inoculate 10 mL of LB (Lennox) media containing 50 pg / mL Kanamycin and 50 pg / mL Apramycin in a 50 mL Falcon tube, yielding the starter

[0414] 17208777 CXB CXB culture. This starter culture was incubated on an inclined rack in a shaking incubator at 30°C at 200 rpm, overnight. The starter culture was then used to inoculate 50 mL of M9 minimal media containing 50 pg / mL Kanamycin, 50 pg / mL Apramycin and 1 mM IPTG (isopropyl-p-D-thiogalactopyranoside) in a 250 mL shake-flask at 2% inoculum, yielding the production culture. This production culture was placed in a shaking incubator at 28°C, shaking at 150 rpm for a total of 14 days, with aliquots taken over several days to assess compound production via LC-MS analysis.

[0415] 5.2.1 - Cloning confirmation

[0416] Figure 11 provides cloning confirmation of a compound of formula (I) using PCR. Three sets of primers were designed: two to bind in regions at both junctions of the gene cluster and adaptor, and one to bind in the middle of the gene cluster. Successful cloning was confirmed by presence of bands at the expected size as shown in the figure.

[0417] 5.3 - LC-MS data acquisition and analysis

[0418] LC-MS data was collected using the same method set out in Example 4, section 4.1.

[0419] 5.3.1 - Results and Identification via LC-MS

[0420] Figures 12a-c show the mass spectrum results obtained from the heterologous expression strain RS-AI48. The mass profiles show the experimental [M+2H]2+, [M-2H+Fe(l 11)]+and [M- 2H+Fe(l 11)+ H]2+ions for a compound of formula (I), which are in agreement with the predicted values as provided in Table 4. Therefore, the results show good experimental agreement between the proposed structure and the theoretical masses and confirm the identify of compound (I).

[0421] This figure also provides a comparison with the LC-MS trace observed for a nonengineered control strain. The LC-MS trace for the non-engineered control strain does not show the presence of the key ion peaks [M+2H]2+, [M-2H+Fe(l 11)]+and [M-2H+Fe(lll)+ H]2+and therefore it can be concluded that a compound of formula (I) was not obtained from the non-engineered control strain.

[0422] 5.4 - Conclusion

[0423] 17208777 CXB CXB A compound of formula (I) was produced via heterologous expression in modified Pseudomonas putida (strain DSM 6125).

[0424] Example 6 - Purification of compound of formula (I)

[0425] Compound of formula (I) obtained in any of the previous examples was purified according to the following method.

[0426] 6.1 - Extraction

[0427] Bacterial culture was extracted with methanol (MeOH) as follows. The culture was concentrated to dryness and extracted with MeOH (1 / 3rdof the volume of the culture) with 15 min sonication in a water bath sonicator. This was repeated three times, and the combined extracts were subjected to centrifugation to remove particulates and then concentrated under vacuum, resulting in a dried crude extract.

[0428] 6.2 - Flash Column Chromatography

[0429] The crude extract was dissolved in 20 mL H2O + 0.1% formic acid (FA), and flash column chromatography was carried out with 2 x 10 mL injections. The column used for this purpose was a Biotage Star C18 D - Duo 100 A 30 pm 60 g. The solvents were H2O for Line A and acetonitrile for Line B. Solvent flow rate was set at 50 mL / min and the following gradient was used:

[0430] For each run, 75 x 17 mL fractions were collected in 16 x 150 mm test tubes and then pooled as 5 x 17 mL to give 15 fractions. These were then concentrated and subjected to LC-MS analysis. Relevant fractions containing compound (I) were combined and dried. Further purification of the recovered compound was performed by preparative HPLC.

[0431] 6.3 - Preparative HPLC

[0432] 17208777 CXB CXB 295 mg of the material from the fractions collected in the previous step was dissolved in 0.5 mL of H2O + 0.1% FA and preparative HPLC was carried out with 470 pL injections. The column used for this purpose was a Luna Omega 5 pm Polar C18 100A, 250 x 21.2 mm. The solvents were H2O+ 0.1% FA for Line A and acetonitrile + 0.1% FA for Line B. Solvent flow rate was set at 20 mL / min and the following gradient was used:

[0433] For each run, 12 x 17 mL fractions were collected for 0 - 10 min to give 12 fractions. These were concentrated and subject to LCMS analysis. Compound (I) was observed in fractions 5 - 7, with fraction 6 containing compound (I) at > 90% purity. Relevant fractions containing compound (I) were combined and dried.

[0434] 6.4 - Results

[0435] 6.4.1 - Purity

[0436] Purity of compound (I) was assessed by analysis of LCMS chromatograms (Figure 13), whereby integration of the peaks observed demonstrated that compound (I) was present at > 90% purity as determined by MS and UV. This was further confirmed by NMR analysis, whereby integration of the 1 H proton signals showed that compound (I) was > 90% purity.

[0437] 6.5 - Conclusion

[0438] Compound (I) was purified via reverse-phase chromatography to achieve >90% purity.

[0439] Example 7 - Fungal Growth Study of Zymoseptoria tritici in planta

[0440] Preventative in planta activity testing of compound (I) against Zymoseptoria tritici in winter wheat plants was conducted as follows. Pots were sown using winter wheat (Triticum aestivum) cultivar JB Diego. Ten seeds were sown into 8 cm diameter pots, with three replicate pots sown per treatment. Once sown, pots were transferred to a controlled environment room and grown at 16°C for approximately 14 days by which point plants had

[0441] 17208777 CXB CXB reached BBCH 12 (two leaves unfolded on the main shoot). BBCH is a scale used to identify the phenological development stages of plants. Treatments were applied when wheat plants were at 12 on the BBCH scale. Five treatments were applied in the screen: compound (I) at 4 different concentrations (300 pg / mL, 100 pg / m, 50 pg / mL and 10 pg / mL), along with a positive control (Imtrex, 50 pg / mL) and a negative control (water). All treatments were applied using a handheld atomiser sprayer with 1 ml of spray solution applied per treatment. Following treatment pots were placed in a fully randomised block design. Plants were inoculated one day after treatment with a spore suspension containing 7x106 conidia / ml. The spore suspension was made up in a 0.05% Tween 20 solution. Each replicate was inoculated to the point of run off (approximately 2 ml) using a handheld atomiser sprayer and then incubated at 18°C under conditions of high humidity for 72 hours, after which plants were grown at 18°C until symptoms expressed.

[0442] Disease assessment was performed 22 days after inoculation. Disease severity was assessed on five plants per replicate pot as a visual assessment of the percentage of the total area where pycnidia were present on the first leaf to emerge, following the visual key illustrated in Figure 15. Six examples of wheat leaves are provided with disease severities ranging from 1% to 75% (areas of disease are represented in black). Differences between treatments were determined through calculation of the least significant difference of the means using Genstat version 24, with analysis using ANOVA. Percentage values were transformed using an angular transformation before statistical analysis was carried out.

[0443] 7.1 - Results

[0444] Figure 14 shows the effect of treatment with Compound (I) on disease caused by Zymoseptoria tritici on winter wheat plants. As can be observed, the compound exhibited dose-dependent disease control. When applied to plants at either 300, 100 or 50 pg / mL, Compound (I) produced a significant reduction (p=0.05) in Zymoseptoria tritici disease severity when compared to the water control. Over the dose range tested (10 pg / mL to 300 pg / mL) there was a near-linear increase in disease control as a function of dose between 10 pg / mL and 100 pg / mL, followed by a gradual-but-incomplete plateau in disease control above 100 ppm. Disease control likely reached a maximum at a concentration between 300-600 pg / mL. Under the conditions of this screen there was no observed phytotoxicity towards young (BBCH 12) winter wheat plants following treatment between 10 and 300

[0445] 17208777 CXB CXB pg / mL. Plants were checked for phytotoxicity just prior to inoculation (24 h after treatment), 72 h after treatment and at the final assessment 23 days after treatment.

[0446] 7.2 - Conclusions

[0447] Compound (I) exhibited statistically significant and commercially applicable control of septoria tritici blotch caused by Z. tritici on wheat plants.

[0448] Example 8 - Bioassay Study of pathogens in vitro

[0449] 8.1 - Agricultural fungal pathogens

[0450] Compound (I) and standards were screened at 10 doses (130, 65, 32, 16, 8, 4, 2, 1, 0.5 and 0.25 pg / mL) with each test combination replicated twice. Compound (I) was initially prepared at a concentration of 65,000 pg / mL in 100% DMSO. Stock solutions (13,000 pg / mL) were then produced for both compound (I) and standards and from these a 1 :2 serial dilution using 100% DMSO created down to 25 pg / mL. From each serial dilution 2 pL was added to an appropriate well in a 96 well plate; an equivalent amount of DMSO was added to control wells. For each pathogen a spore suspension (containing 1,000 spores / mL) was produced in GPM broth and 198 pL of this added to the appropriate wells on the 96 well plate to give the required final well concentrations in 1% DMSO. Plate absorbance was read at 405 nm immediately after plate set up and then again after plates were incubated for 4 days at 18°C. IC50 values for each compound and pathogen were calculated based on a comparison of growth in the control and test wells. The doseresponse curve was fit using a four-parameter logistic model 'LL.4' (Ritz, C., Baty, F., Streibig, J.C., and Gerhard, D. (2015). Dose-Response Analysis Using R. PLoS ONE, 10(12), e0146021). The IC50 was determined as the minimum concentration of test compound (i.e. compound (I)) resulting in >50% inhibition when compared to the positive control..

[0451] 17208777 CXB CXB

[0452] Table 7 IC50 values, % growth inhibition plateau and rate at which plateau begins, across a range of agricultural fungal and fungal-like pathogens

[0453] Table 8 IC50 values, % growth inhibition plateau and rate at which plateau begins across susceptible and resistant Zymoseptoria tritici strains.

[0454] 17208777 CXB CXB

[0455] Table 9. Source information for pathogen samples screened.

[0456] 8.1.1 - Results and conclusions

[0457] As shown by the results obtained in section 8.1 and Figures 16 and 17, Compound (I) exhibits broad inhibition against a panel of commercially relevant agricultural pathogens, indicating it has a mode of action that can be applied effectively in a broad number of key agricultural fungicide markets.

[0458] Figure 16 illustrates dose response curves of compound (I) against M. nivale, P. cactorum, V. dahliae and V. inaequalis from an absorbance-based assay. IC50 values are derivable from these results and are detailed in Table 7. The growth inhibition plateaus at 39% and 30% and 51% for P. cactorum, V. daliae and V. inaequalis, respectively. The growth inhibition of M. nivale does not plateau over the tested concentration range of Compound (I), however, indicating higher growth inhibition is achievable at higher concentrations of Compound (I).

[0459] Figure 17 illustrates dose response curves of compound (I) against three Zymoseptoria tritici strains from an absorbance-based assay: a susceptible strain, a succinate dehydrogenase inhibitor (SDHI)-resistant strain, and a demethylation inhibitor (DMI)- resistant strain. IC50 values are derivable from these results and are detailed in Table 8. All three dose response curves plateau at approximately 70-80%, and have comparable IC50 values. The three control dose response curves (bottom row) behaved as expected.

[0460] Without wishing to be bound by theory, it is believed that the bioactivity of Compound (I) against the agricultural fungal pathogens Zymoseptoria tritici, Venturia inaequalis, Microdochium nivale, Botrytis cinerea, Verticillium dahliae and Phytophthora cactorum may be associated with differences in their iron-acquisition mechanisms and susceptibility to siderophore competition.

[0461] The strong or partial inhibition observed at higher concentrations of Compound (I) for Zymoseptoria tritici (77% at 32 pg / mL), Microdochium nivale (64 % at 130 pg / mL) and Venturia inaequalis (52 % at 65 pg / mL) suggests that these fungal pathogens possess

[0462] 17208777 CXB CXB limited or specialized siderophore biosynthetic capacity and reduced iron-uptake redundancy, rendering them more vulnerable to iron sequestration.

[0463] Phytophthora cactorum, exhibits partial inhibition even at low concentrations (39 % at 8 pg / mL) which suggests that this pathogen is sensitive to siderophore-mediated iron limitation. Without wishing to be bound by theory, it is believed that this may be due to a lack of classical siderophore pathways and thus a predominant reliance on reductive iron uptake.

[0464] In contrast, Verticillium dahliae and Botrytis cinerea exhibit weaker partial inhibition at higher concentrations of Compound (I) (V. dahliae 30 % at 65 ppm; B. cinerea 7 % at 32 pg / mL). These observations are consistent with moderate siderophore production and greater redundancy in iron-acquisition systems.

[0465] The consistent IC50 values observed across Zymoseptoria tritici strains, including a susceptible strain, a succinate dehydrogenase inhibitor (SDHI)resistant strain, and a demethylation inhibitor (DM I) resistant strain, indicate that Compound (I) acts via a mechanism distinct from succinate dehydrogenase or demethylation inhibition. Without being bound by theory, Compound (I) is believed to exert its activity through a siderophore- related iron-starvation pathway and may additionally act via intracellular fungicidal effects following uptake (a “Trojan-horse” mechanism).

[0466] 8.2 - Human bacterial and fungal pathogens

[0467] Antibacterial testing was performed following CLSI guidelines (M07-Ed12) using broth microdilution methods. Compound (I) was prepared at 100x maximum testing concentration. These stocks were serially diluted 1:1 in the relevant solvent to produce a 100x master plate. Ciprofloxacin or meropenem were included as quality control compounds. Positive (growth) and negative (sterility) controls were also included. 100x master stocks were transferred into iron depleted cation-adjusted Mueller-Hinton broth in a flat-bottom 96-well plate to yield test articles at twice their required final test concentration. Each strain to be tested was grown on appropriate agar at 37°C overnight. A bacterial suspension was prepared from each strain equivalent to a 0.5 McFarland suspension. This suspension was diluted in relevant medium to produce a final inoculum level of 2-8 * 105 cfu / mL and added to the test plates. Plates were incubated at 37°C for 16-20 hours. After

[0468] 17208777 CXB CXB incubation, growth was assessed on a microplate reader (absorbance 600 nm). The concentration resulting in 50% growth inhibition was calculated from absorbance readings.

[0469] Antifungal susceptibility testing for yeast strains was performed following ELICAST guidelines (E.Def 7.4). C. krusei ATCC 6258 was included as a quality control strain. Amphotericin B was included as a comparator and quality control compound. Positive (growth) and negative (sterility) controls were also included. Compound (I) was prepared at 100x highest test concentration, serially diluted and added to 2x assay medium (Roswell Park Memorial Institute 1640 medium + 2% glucose + 0.165M MOPS) in a flat-bottom 96- well plate to result in test articles being at twice the required test concentration. Strains were grown on Sabouraud dextrose agar at 35°C overnight (48 hours for Cryptococcus neoformans (HA99)). A single colony suspension was prepared in sterile water, equivalent to a 0.5 McFarland standard. This suspension was further diluted in sterile water to produce a final inoculum level of between 1-5 x 105 cfu / mL. Adjusted inoculum was added to the test plates and plates were incubated at 35°C for 48 hours. After incubation, a growth was assessed using a microplate reader (absorbance 530 nm). A “discrete IC50” was defined as the lowest tested concentration of Compound (I) that produced >50% inhibition relative to the positive control.

[0470] Table 10. Discrete IC50 values for Compound (I) across a range of human bacterial and fungal pathogens.

[0471] 8.2.1 - Conclusions

[0472] As shown by the results obtained in section 8.2, Compound (I) exhibits broad inhibition against a panel of commercially relevant fungal and bacterial human pathogens, indicating

[0473] 17208777 CXB CXB it has a mode of action that can be applied effectively in a broad number of key healthcare markets.

[0474] Without wishing to be bound by theory, it is believed that the strong bioactivity of Compound (I) to Cryptococcus neoformans (HA99), Candida krusei ATCC 6258, Klebsiella pneumoniae ATCC 43816, and Staphylococcus aureus ATCC 29213 reflects the high siderophore susceptibility of these specific pathogens, which spans both fungal and bacterial pathogens.

[0475] Example 9 - Toxicity Studies

[0476] 9.1 - In vitro cellular toxicity (cytotoxicity)

[0477] HepG2 cells were plated on appropriate tissue culture treated plates. The cells were dosed with test compound for 72 hours at a range of concentrations as set out in Table 11. At the end of the incubation period, the cells were lysed to release ATP. The plates were then scanned using a plate reader.

[0478] Table 11. Summary of experimental parameters for cellular toxicity assay.

[0479] Cellular ATP is a direct readout of cell health and hence compound toxicity. Healthy cells are metabolically active and generate cellular ATP, therefore, a decrease in metabolically active cells is accompanied by a decrease in the level of cellular ATP.

[0480] 9.1.1 - Results

[0481] 17208777 CXB CXB

[0482] Table 12. Summary of cellular toxicity for compound (I) and two control compounds: carbonyl cyanide 3-chlorophenylhydrazone and chlorpromazine. MEC is the Minimum effective concentration that significantly crosses vehicle control threshold. AC50 is the concentration at which 50% maximum effect is observed for each cell health parameter. represents the direction of response; an upward response may indicate either cell proliferation, metabolic stimulation or assay artefact; a downward response indicates lower ATP levels due to fewer metabolically active cells, and hence higher activity. NR stands for No response observed. MR stands for Maximum response (ratio of control), defined as the largest observed effect (i.e. change in ATP levels) caused by the compound in the assay relative to control conditions, and indicates the maximum level of toxicity observed at the concentrations tested. R2is a statistical measure of how well the regression model fits the data and is defined as 1 minus (sum of squared residuals (errors) I total sum of squared residuals). High R2values (i.e. above 0.90) indicate that the model explains most of the variability in the data and provides a strong, reliable fit to the observed trend.

[0483] As shown in Figure 18, Compound (I) maintains a ratio of control of approximately 1 across the entire concentration range tested, indicating no change in the number of metabolically active, healthy cells relative to the untreated control. Compound (I) therefore shows no cellular toxicity within the tested range (0-100 pM). In contrast, the positive control compounds carbonyl cyanide 3-chlorophenylhydrazone and chlorpromazine show reduced metabolic activity at higher concentrations, reflected by decreased ratios of control and consistent with known cellular toxicity. High R2values (i.e. above 0.90) indicate that the model explains most of the variability in the data and provides a strong, reliable fit to the observed trend.

[0484] 9.2 - In vitro mitochondrial toxicity

[0485] 17208777 CXB CXB HepG2 cells were plated on appropriate tissue culture treated plates at a density of 6000 cells, 25pL per well. The cells were dosed with test compound at a range of concentrations as set out in Table 13 below. 4-6 hrs before dosing, the media was replaced with Dulbecco’s Modified Eagle’s Medium (DM EM) containing either galactose or glucose supplemented with 10% foetal bovine serum and antibiotics. At the end of the incubation period, the cells were loaded with the relevant dye / antibody for each cell health marker. The plates were then scanned using a microplate luminescence reader.

[0486] Table 13. Summary of experimental parameters for mitochondrial toxicity assay.

[0487] 9.2.1 - Determination of mitochondrial toxicity

[0488] Mitochondrial toxicity is determined from the relative sensitivity of cells grown in medium containing either galactose or glucose to the test compound.

[0489] The AC50 was calculated from a curve fit to determine percent survival of compound (I) and two control compounds. The fold change was calculated from AC50 curve fit data by comparison with cells dosed in glucose or galactose. A greater than 2-fold shift between glucose and galactose indicates the compound is considered to be a mitochondrial toxicant.

[0490] 9.2.2 - Results

[0491] 17208777 CXB CXB

[0492] Table 14. Summary of mitochondrial toxicity for compound (I) and two control compounds: carbonyl cyanide 3-chlorophenylhydrazone and chlorpromazine. AC50 is the concentration at which 50% maximum effect is observed for each cell health parameter. indicates the direction of response; an upward response may indicate increased mitochondrial activity via mitochondrial uncoupling (i.e. increased ATP turnover) or a compensatory metabolic response indicative of mild stress; a downward response indicates lower mitochondrial ATP output or impaired mitochondrial function and hence mitochondrial toxicity. NR stands for “No Response” observed. R2is a statistical measure of how well the regression model fits the data and is defined as 1 minus (sum of squared residuals (errors) I total sum of squared residuals). High R2values (i.e. above 0.90) indicate that the model explains most of the variability in the data and provides a strong, reliable fit to the observed trend.

[0493] Figure 19 shows that Compound (I) maintains an average ratio of control of approximately 1 across the tested concentrations in both glucose- and galactose-containing media. No individual datapoints fall outside the vertical range defined by the dotted significance thresholds, indicating no statistically significant perturbation of mitochondrial activity at any concentration of Compound (I). Accordingly, Compound (I) demonstrates no mitochondrial toxicity within the tested range (0-100 pM).

[0494] In contrast, the positive control compounds behaved as expected. Rotenone and chlorpromazine show significant decreases in mitochondrial activity at higher concentrations in the presence of glucose, indicating both are cellular toxicants. Only rotenone demonstrates true mitochondrial toxicity, as evidenced by a statistically significant 231-fold shift in AC50 in the presence of galactose relative to glucose. Chlorpromazine, which does not show a substantial AC50 shift between glucose and galactose, is therefore not classified as a mitochondrial toxicant in this assay.

[0495] 9.3 - Conclusions

[0496] 17208777 CXB CXB The horizontal lines shown in figures 18 and 19a), and b), for Compound (I) demonstrate that Compound (I) exhibits no human HepG2 cellular or mitochondrial toxicity up to 100 pM. Selectivity index is a key parameter used to determine the therapeutic potential of a compound and is defined as AC50 (toxicity) I IC50 (efficacy). The lack of toxicity combined with the high efficacy of Compound (I) against a number of bacterial and fungal pathogens, as evidenced in Examples 1 , 2, 7 and 8, equates to a high selectivity index and thus good therapeutic potential. For example, Compound (I) exhibits a selectivity index of greater than 60x for bacterial healthcare pathogen A. baumannii and of greater than 130x for fungal agricultural pathogen Z. tritici.

[0497] Example 10 - In silico toxicity screen

[0498] The toxicological assessment of compound (I) was performed using in silico Expert System DEREK Nexus, and two QSAR packages (T.E.S.T. and four VEGA models).

[0499] Compound (I) is predicted to be non-mutagenic and have no endocrine activity, overall suggesting a safe toxicology profile.

[0500] 17208777 CXB CXB

Claims

1. - 87 -CLAIMS1. A compound of formula (I):wherein R1is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;R2is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;wherein R12is selected from -H and -OH, and n is selected from 0 to 3;R4is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;R5isor tautomers thereof, wherein m is selected from 1 to 5;R6is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;R7is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl;R8is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one -OH group;17208777 CXB CXB- 88 -R9is selected fromwherein R13is selected from -H and Ci-Ce-alkyl, and p is selected from 1 to 5;R10is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl; andR11is selected from -H and Ci-Ce-hydrocarbyl optionally substituted with at least one group selected from -OH, halo, formyl and acetyl.

2. The compound of formula (I) according to claim 1 , wherein R1, R2and R8are independently selected from -H and Ci-Ce-alkyl optionally substituted with at least one -OH group.

3. The compound of formula (I) according to claim 1 or claim 2, wherein R1, R2and R8are independently selected from -H and Ci-Cs-alkyl.

4. The compound of formula (I) according to any one of the preceding claims, wherein R4, R6, R7, R10and R11are independently selected from -CH(OH)CH3 and -CH2OH.

5. The compound of formula (I) according to claim 4, wherein R6is -CH2OH and / or R4, R7, R10and R11are -CH(OH)CH3.

6. The compound of formula (I) according to any one of the preceding claims, wherein n is 0, and p is 3.

7. The compound of formula (I) according to any one of the preceding claims, wherein8. The compound of formula (I) according to any one of the preceding claims, wherein m is 3.17208777 CXB CXB- 89 -9. The compound of formula (I) according to any one of the preceding claims, wherein10. The compound of formula (I) according to any one of the preceding claims, wherein the compound of formula (I) istautomers or salts thereof.

11. A composition comprising the compound of formula (I) according to any one of claims 1-10 as an active ingredient and, optionally, an acceptable carrier or excipient.

12. A use of the compound of formula (I) according to any one of claims 1-10, or the composition of claim 11, as an antimicrobial agent.

13. The use according to claim 12 wherein the antimicrobial agent is as an antifungal agent.

14. The use according to claim 12 wherein the antimicrobial agent is an antibacterial agent.

15. The use according to claim 12 or 13, wherein the compound is effective against an oomycete or water mold, such as an oomycete of the family Peronosporaceae (e.g Phytopthora infestans or Phytophthora cactorum).

16. The use according to claim 12 or 13, wherein the compound is effective against a filamentous fungus, such as a fungus of the family Mycosphaerellaceae (e.g. Zymoseptoria tritici).17208777 CXB CXB- 90 -17. The compound of formula (I) according to any one of claims 1-10, or the composition of claim 11, for use in treating a bacterial or fungal disease or infection in a subject.

18. The compound of formula (I) or the composition for use according to claim 17 wherein the subject is human.

19. The compound of formula (I) or the composition for use according to claim 17 or 18 wherein the subject is: a) suffering from a bacterial or fungal disease or infection; and / or b) immunocompromised.

20. The compound of formula (I) or the composition for use according to any one of claims 17-19, wherein the bacterial disease or infection is selected from a skin and soft tissue infection, such as a wound infection, a urinary tract infection, a lung infection, such as pneumonia, meningitis, or bacteremia.

21. The compound of formula (I) or the composition for use according to any one of claims 17-20, wherein the compound of formula (I) is effective against gram-negative bacteria, such as a bacterium of the family Moraxellaceae (e.g. Acinetobacter baumannii), and / or a bacterium of the family Enterobacteriaceae (e.g. Klebsiella pneumoniae), and / or wherein the compound of formula (I) is effective against gram-positive bacteria, such as a bacterium of the family Staphylococcaceae (e.g. Staphylococcus aureus), and / or wherein the compound of formula (I) is effective against yeast, such as Cryptococcus neoformans.

22. A method for treating a plant to control a disease, the method comprising applying an effective amount of the compound of formula (I) according to any one of claims 1-10, or the composition of claim 11, to the plant, or a part of the plant.

23. The method of claim 22, wherein the plant is wheat, potato or tomato.

24. A method for producing the compound of formula (I) according to any one of claims 1-10 comprising synthesising the compound of formula (I) from a biosynthetic gene cluster17208777 CXB CXB- 91 - encoding the peptides of SEQ ID NOs: 1-31 , or peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1-31.

25. A biosynthetic gene cluster encoding at least 10 peptides of any one of SEQ ID NOs: 1-31 , or peptides of 80%, 85%, 90%, 95%, 97%, or 99% identity to SEQ ID NOs: 1- 31.17208777 CXB CXB

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