Genomic virulence features of Beauveria bassiana as a biocontrol agent for the mountain pine beetle population.

BACKGROUND: The mountain pine beetle, Dendroctonus ponderosae, is an irruptive bark beetle that causes extensive mortality to many pine species within the forests of western North America. Driven by climate change and wildfire suppression, a recent mountain pine beetle (MPB) outbreak has spread across more than 18 million hectares, including areas to the east of the Rocky Mountains that comprise populations and species of pines not previously affected. Despite its impacts, there are few tactics available to control MPB populations. Beauveria bassiana is an entomopathogenic fungus used as a biological agent in agriculture and forestry and has potential as a management tactic for the mountain pine beetle population. This work investigates the phenotypic and genomic variation between B. bassiana strains to identify optimal strains against a specific insect. RESULTS: Using comparative genome and transcriptome analyses of eight B. bassiana isolates, we have identified the genetic basis of virulence, which includes oosporein production. Genes unique to the more virulent strains included functions in biosynthesis of mycotoxins, membrane transporters, and transcription factors. Significant differential expression of genes related to virulence, transmembrane transport, and stress response was identified between the different strains, as well as up to nine-fold upregulation of genes involved in the biosynthesis of oosporein. Differential correlation analysis revealed transcription factors that may be involved in regulating oosporein production. CONCLUSION: This study provides a foundation for the selection and/or engineering of the most effective strain of B. bassiana for the biological control of mountain pine beetle and other insect pests populations.

Simplified cloning and isolation of peptides from "sandwiched" SUMO-peptide-intein fusion proteins.

BACKGROUND: Some peptides are targets for degradation when heterologously expressed as fusion proteins in E. coli, which can limit yields after isolation and purification. We recently reported that peptide degradation may be prevented by production of a "sandwiched" SUMO-peptide-intein (SPI) fusion protein, which protects the target peptide sequence from truncation and improves yield. This initial system required cloning with two commercially available vectors. It used an N-terminal polyhistidine tagged small ubiquitin-like modifier (SUMO) protein and a C-terminal engineered Mycobacterium xenopii DNA Gyrase A intein with an inserted chitin binding domain (CBD) to create "sandwiched" fusion proteins of the form: His6-SUMO-peptide-intein-CBD. However, the major drawback of this previously reported fusion protein "sandwich" approach is the increased time and number of steps required to complete the cloning and isolation procedures, relative to the simple procedures to produce recombinant peptides in E. coli from a single (non-"sandwiched") fusion protein system. RESULTS: In this work we generate the plasmid pSPIH6, which improves upon the previous system by encoding both the SUMO and intein proteins and allows facile construction of a SPI protein in a single cloning step. Additionally, the Mxe GyrA intein encoded in pSPIH6 contains a C-terminal polyhistidine tag, resulting in SPI fusion proteins of the form: His6-SUMO-peptide-intein-CBD-His6. The dual polyhistidine tags greatly simplify isolation procedures compared to the original SPI system, which we have here demonstrated with two linear bacteriocin peptides: leucocin A and lactococcin A. The yields obtained for both peptides after purification were also improved compared to the previous SPI system as a result of this streamlined protocol. CONCLUSIONS: This modified SPI system and its simplified cloning and purification procedures described here may be generally useful as a heterologous E. coli expression system to obtain pure peptides in high yield, especially when degradation of the target peptide is an issue.

New insights into natural rubber biosynthesis from rubber-deficient lettuce mutants expressing goldenrod or guayule cis-prenyltransferase.

Lettuce produces natural rubber (NR) with an average Mw of > 1 million Da in laticifers, similar to NR from rubber trees. As lettuce is an annual, self-pollinating, and easily transformable plant, it is an excellent model for molecular genetic studies of NR biosynthesis. CRISPR/Cas9 mutagenesis was optimized using lettuce hairy roots, and NR-deficient lettuce was generated via bi-allelic mutations in cis-prenyltransferase (CPT). This is the first null mutant of NR deficiency in plants. In the CPT mutant, orthologous CPT counterparts from guayule (Parthenium argentatum) and goldenrod (Solidago canadensis) were expressed under a laticifer-specific promoter to examine how the average Mw of NR is affected. No developmental defects were observed in the NR-deficient mutants. The lettuce mutants expressing guayule and goldenrod CPT produced 1.8 and 14.5 times longer NR, respectively, than the plants of their origin. This suggests that, although goldenrod cannot synthesize a sufficiently lengthy NR, goldenrod CPT has the catalytic competence to produce high-quality NR in the cellular context of lettuce laticifers. Thus, CPT alone does not determine the length of NR. Other factors, such as substrate concentration, additional proteins, and/or the nature of protein complexes including CPT-binding proteins, influence CPT activity in determining NR length.

Beauveria bassiana exhibits strong virulence against Dendroctonus ponderosae in greenhouse and field experiments.

The mountain pine beetle (MPB) has infested over 16 million hectares of pine forests in western Canada, killing over 50% of mature lodgepole pine, Pinus contorta, in British Columbia alone. There are few tools available to manage irruptive bark beetle populations and to mitigate tree mortality. Beauveria bassiana is an entomopathogenic fungus that causes mortality to several bark beetle species. However, the potential for B. bassiana as a biocontrol agent against pine beetle populations is unknown. We selected three strains of B. bassiana from several culture collections and evaluated their conidial stability under cold storage, in planta (greenhouse, and pine bolts) and in natura (forest stand, pine bolts, and live pines) conditions. The stability assays showed that all fungal strains maintained a minimum effective conidial yield through the assay durations (3-12 weeks). In addition, we adapted a biphasic liquid-solid fermentation approach for the large-scale production of conidial biomass, yielding up to a 100-fold increase in production. In greenhouse virulence assays, the mean lethal time of MPBs was reduced to 3-4 days upon treatment with B. bassiana, where high B. bassiana-associated mycosis was also observed. Furthermore, the application of B. bassiana formulation substantially affected the gallery network of MPBs in bolts in the field, resulting in shorter larval galleries and significantly reduced offspring production. Indeed, high titer treatments reduced the mean larvae per gallery to virtually zero. Together these results demonstrate that B. bassiana may be a viable biocontrol tool to reduce mountain pine beetle populations in pine forests in western Canada. KEY POINTS: • Three B. bassiana strains identified to be stable at various test conditions. • Large-scale conidial biomass production using liquid-solid biphasic fermentation. • Reproductive success of D. ponderosae significantly reduced by B. bassiana formulation.

Composition and activity of antifungal lipopeptides produced by Bacillus spp. in daqu fermentation.

Daqu is a solid-state fermentation and saccharification starter for the Chinese liquor baijou. During the daqu stage, amylolytic and proteolytic enzymes are produced by Bacillus and fungi. Bacillus spp. also produce lipopeptides with a broad spectrum of antimicrobial activities but direct evidence for their impact on community assembly in daqu is lacking. This study aimed to study the interaction between Bacillus spp. and fungi in daqu models. The antifungal activity of surfactin, fengycin, and iturin A was initially assessed in vitro. Iturin A displayed the strongest antifungal activity (MIC = 10-50 mg/L). In situ antifungal activity of B. amyloliquefaciens and B. velezensis against molds was observed in a simple daqu model inoculated with single strains of Bacillus species. Formation of lipopeptides in situ was supported by quantification of mRNA encoding for enzymes for surfactin, fengycin, and iturin A biosynthesis. In situ antifungal activity of Bacillus species was also observed in a complex daqu model that was inoculated with 8 bacterial or fungal strains plus one of the three strains of Bacillus. A relationship of lipopeptides to in situ antifungal activity was further supported by detection of the lipopeptides by liquid chromatography coupled to mass spectrometry. Both results indicated that B velezensis FUA2155 had higher antifungal activity in the daqu model, and was the only strain that produced multiple iturin A congeners in situ. Taken together, this study provides evidence that production of lipopeptides by Bacillus species in daqu may impact community assembly and hence product quality.

Ring-opening reactions for the solid-phase synthesis of nisin lipopeptide analogues.

Three lipopeptide analogues of the lantibiotic nisin A have been synthesised on-resin using Fmoc-SPPS techniques to investigate the structure-activity relationship of the A and B ring of these types of lanthipeptides. Lanthionine and methyllanthionine macrocycles were incorporated using orthogonally protected residues for on-resin cyclisation. Unsaturated dehydroalanine and, for the first time, dehydrobutyrine were synthesised on-resin from their cysteine derivatives. However, none of the synthetic or semi-synthetic lipopeptide analogues of nisin showed inhibitory activity towards bacterial strains that are normally sensitive to nisin.

Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs.

Abdominal aortic aneurysm (AAA) remains the second most frequent vascular disease with high mortality but has no approved medical therapy. We investigated the direct role of apelin (APLN) in AAA and identified a unique approach to enhance APLN action as a therapeutic intervention for this disease. Loss of APLN potentiated angiotensin II (Ang II)-induced AAA formation, aortic rupture, and reduced survival. Formation of AAA was driven by increased smooth muscle cell (SMC) apoptosis and oxidative stress in Apln-/y aorta and in APLN-deficient cultured murine and human aortic SMCs. Ang II-induced myogenic response and hypertension were greater in Apln-/y mice, however, an equivalent hypertension induced by phenylephrine, an α-adrenergic agonist, did not cause AAA or rupture in Apln-/y mice. We further identified Ang converting enzyme 2 (ACE2), the major negative regulator of the renin-Ang system (RAS), as an important target of APLN action in the vasculature. Using a combination of genetic, pharmacological, and modeling approaches, we identified neutral endopeptidase (NEP) that is up-regulated in human AAA tissue as a major enzyme that metabolizes and inactivates APLN-17 peptide. We designed and synthesized a potent APLN-17 analog, APLN-NMeLeu9-A2, that is resistant to NEP cleavage. This stable APLN analog ameliorated Ang II-mediated adverse aortic remodeling and AAA formation in an established model of AAA, high-fat diet (HFD) in Ldlr-/- mice. Our findings define a critical role of APLN in AAA formation through induction of ACE2 and protection of vascular SMCs, whereas stable APLN analogs provide an effective therapy for vascular diseases.

Tityus serrulatus scorpion venom as a potential drug source for Chagas' disease: Trypanocidal and immunomodulatory activity.

Current chemical therapies for Chagas Disease (CD) lack ability to clear Trypanosoma cruzi (Tc) parasites and cause severe side effects, making search for new strategies extremely necessary. We evaluated the action of Tityus serrulatus venom (TsV) components during Tc infection. TsV treatment increased nitric oxide and pro-inflammatory cytokine production by Tc-infected macrophages (MØ), decreased intracellular parasite replication and trypomastigotes release, also triggering ERK1/2, JNK1/2 and p38 activation. Ts7 demonstrated the highest anti-Tc activity, inducing high levels of TNF and IL-6 in infected MØ. TsV/Ts7 presented synergistic effect on p38 activation when incubated with Tc antigen. KPP-treatment of MØ also decreased trypomastigotes releasing, partially due to p38 activation. TsV/Ts7-pre-incubation of Tc demonstrated a direct effect on parasite decreasing MØ-trypomastigotes releasing. In vivo KPP-treatment of Tc-infected mice resulted in decreased parasitemia. Summarizing, this study opens perspectives for new bioactive molecules as CD-therapeutic treatment, demonstrating the TsV/Ts7/KPP-trypanocidal and immunomodulatory activity during Tc infection.

Improved Synthesis of a Cyclic Glutamine Analogue Used in Antiviral Agents Targeting 3C and 3CL Proteases Including SARS-CoV-2 Mpro.

An intermediate in the synthesis of numerous antiviral protease inhibitors is the glutamine analogue, (3S)-pyrrolid-2-one-3-yl-l-alanine. Preparations of compounds based on this pharmacophore are hindered by the lack of a reliably high yielding synthesis of protected forms of this amino acid. We describe an improved scalable route with readily available reagents and facile purification. This methodology employs γ-allylation of dimethyl N-BocGlu, further Boc N-protection, OsO4-periodate oxidation, O-Me oxime formation, and RaNi-catalyzed hydrogenolysis with concomitant cyclization under basic conditions.

Selection of entomopathogenic fungus Beauveria bassiana (Deuteromycotina: Hyphomycetes) for the biocontrol of Dendroctonus ponderosae (Coleoptera: Curculionidae, Scolytinae) in Western Canada.

The mountain pine beetle, Dendroctonus ponderosae, has infested over ~16 Mha of pine forests in British Columbia killing >50% of mature lodgepole pine, Pinus contorta, trees in affected stands. At present, it is functionally an invasive species in Alberta, killing and reproducing in evolutionarily naïve populations of lodgepole pine (P. contorta), novel jack pine (P. banksiana), and their hybrids. The entomopathogenic fungus Beauveria bassiana has shown some potential as a biocontrol agent of several bark beetle species. In this study, nine isolates of B. bassiana were examined for insect virulence characteristics, including conidiation rate, pigmentation, and infection rate in laboratory-reared D. ponderosae, to assess for their potential as biocontrol agents. The strains were categorized into three phenotypic groups based on pigmentation, conidial density, and myceliation rate. Virulence screening utilizing insect-based agar medium (D. ponderosae and European honeybee Apis mellifera carcasses) revealed no difference in selection of fungal growth. However, infection studies on D. ponderosae and A. mellifera showed contrasting results. In vivo A. mellifera infection model revealed ~5% mortality, representing the natural death rate of the hive population, whereas laboratory-reared D. ponderosae showed 100% mortality and mycosis. The LT50 (median lethal time 50) ranges from 2 to 5 ± 0.33 days, and LT100 ranges from 4 to 6 ± 0.5 days. We discuss the selective advantages of the three phenotypic groups in terms of virulence, pigmentation, conidial abundance, and tolerance to abiotic factors like UV and host tree monoterpenes. These results can further provide insights into the development of several phenotypically diverse B. bassiana strains in controlling the spread of the invasive D. ponderosae in Western Canada. KEY POINTS: • Three B. bassiana morphotype groups have been demonstrated to kill D. ponderosae. • A range of effective lethal times (LT50 and LT100) was established against D. ponderosae. • Variable tolerance to UV light and pine monoterpenes were observed in B. bassiana.

Moving Pieces in a Cellular Puzzle: A Cryptic Peptide from the Scorpion Toxin Ts14 Activates AKT and ERK Signaling and Decreases Cardiac Myocyte Contractility via Dephosphorylation of Phospholamban.

Cryptic peptides (cryptides) are biologically active peptides formed after proteolysis of native precursors present in animal venoms, for example. Proteolysis is an overlooked post-translational modification that increases venom complexity. The tripeptide KPP (Lys-Pro-Pro) is a peptide encrypted in the C-terminus of Ts14-a 25-mer peptide from the venom of the Tityus serrulatus scorpion that has a positive impact on the cardiovascular system, inducing vasodilation and reducing arterial blood pressure of hypertensive rats among other beneficial effects. A previous study reported that KPP and its native peptide Ts14 act via activation of the bradykinin receptor B2 (B2R). However, the cellular events underlying the activation of B2R by KPP are unknown. To study the cell signaling triggered by the Ts14 cryptide KPP, we incubated cardiac myocytes isolated from C57BL/6 mice with KPP (10-7 mol·L-1) for 0, 5, or 30 min and explored the proteome and phosphoproteome. Our results showed that KPP regulated cardiomyocyte proteins associated with, but not limited to, apoptosis, muscle contraction, protein turnover, and the respiratory chain. We also reported that KPP led to AKT phosphorylation, activating AKT and its downstream target nitric oxide synthase. We also observed that KPP led to dephosphorylation of phospholamban (PLN) at its activation sites (S16 and T17), leading to reduced contractility of treated cardiomyocytes. Some cellular targets reported here for KPP (e.g., AKT, PLN, and ERK) have already been reported to protect the cardiac tissue from hypoxia-induced injury. Hence, this study suggests potential beneficial effects of this scorpion cryptide that needs to be further investigated, for example, as a drug lead for cardiac infarction.

Dissecting the Binding Interactions of Teixobactin with the Bacterial Cell-Wall Precursor Lipid†II.

The prevalence of life-threatening, drug-resistant microbial infections has challenged researchers to consider alternatives to currently available antibiotics. Teixobactin is a recently discovered "resistance-proof" antimicrobial peptide that targets the bacterial cell wall precursor lipid II. In doing so, teixobactin exhibits potent antimicrobial activity against a wide range of Gram-positive organisms. Herein we demonstrate that teixobactin and several structural analogues are capable of binding lipid II from both Gram-positive and Gram-negative bacteria. Furthermore, we show that when combined with known outer membrane-disrupting peptides, teixobactin is active against Gram-negative organisms.

Catalytic mechanism and properties of pyridoxal 5'-phosphate independent racemases: how enzymes alter mismatched acidity and basicity.

Covering: up to March 2019 Amino acid racemases and epimerases are key enzymes that invert the configuration of common amino acids and supply many corresponding d-isomers in living organisms. Some d-amino acids are inherently bioactive, whereas others are building blocks for important biomolecules, for example lipid II, the bacterial cell wall precursor. Peptides containing them have enhanced proteolytic stability and can act as important recognition elements in mammalian systems. Selective inhibition of certain amino acid racemases (e.g. glutamate racemase) is believed to offer a promising target for new antibacterial drugs effective against pathogens resistant to current antibiotics. Many amino acid racemases employ imine formation with pyridoxal phosphate (PLP) as a cofactor to accelerate the abstraction of the alpha proton. However, the group reviewed herein achieves racemization of free amino acids without the use of cofactors or metals, and uses a thiol/thiolate pair for deprotonation and reprotonation. All bacteria and higher plants contain such enzymes, for example diaminopimelate epimerase, which is required for lysine biosynthesis in these organisms. This process cannot be accomplished without an enzyme catalyst as the acidities of a thiol and the substrate α-hydrogen are inherently mismatched by at least 10 orders of magnitude. This review describes the structural and mechanistic studies on PLP-independent racemases and the evolving view of key enzymatic machinery that accomplishes these remarkable transformations.

Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II.

Tridecaptin A1 (TriA1) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA1 exerts its bactericidal effect by binding to the bacterial cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. Biochemical and biophysical assays show that binding to the Gram-negative variant of lipid II is required for membrane disruption and that only the proton gradient is dispersed. The NMR solution structure of TriA1 in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA1-lipid II complex. These results suggest that TriA1 kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.

Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.

Diacylglycerol acyltransferase 1 (DGAT1) is an integral membrane enzyme catalyzing the final and committed step in the acyl-coenzyme A (CoA)-dependent biosynthesis of triacylglycerol (TAG). The biochemical regulation of TAG assembly remains one of the least understood areas of primary metabolism to date. Here, we report that the hydrophilic N-terminal domain of Brassica napus DGAT1 (BnaDGAT11-113) regulates activity based on acyl-CoA/CoA levels. The N-terminal domain is not necessary for acyltransferase activity and is composed of an intrinsically disordered region and a folded segment. We show that the disordered region has an autoinhibitory function and a dimerization interface, which appears to mediate positive cooperativity, whereas the folded segment of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA. Under increasing acyl-CoA levels, the binding of acyl-CoA with this noncatalytic site facilitates homotropic allosteric activation. Enzyme activation, on the other hand, is prevented under limiting acyl-CoA conditions (low acyl-CoA-to-CoA ratio), whereby CoA acts as a noncompetitive feedback inhibitor through interaction with the same folded segment. The three-dimensional NMR solution structure of the allosteric site revealed an α-helix with a loop connecting a coil fragment. The conserved amino acid residues in the loop interacting with CoA were identified, revealing details of this important regulatory element for allosteric regulation. Based on these results, a model is proposed illustrating the role of the N-terminal domain of BnaDGAT1 as a positive and negative modulator of TAG biosynthesis.

Dess-Martin periodinane oxidative rearrangement for preparation of α-keto thioesters.

A Dess-Martin Periodinane (DMP) mediated oxidative rearrangement reaction was uncovered. The reaction proceeds via oxidation of a ß-hydroxy thioester to a ß-keto thioester, followed by an α-hydroxylation and then further oxidation to form a vicinal thioester tricarbonyl. This product then rearranges, extruding CO2, to form an α-keto product. The mechanism of the rearrangement was elucidated using 13C labelling and analysis of the intermediates as well as the products of the reaction. This efficient process allows for easy preparation of α-keto thioesters which are potential intermediates in the synthesis of pharmaceutically important heterocyclic scaffolds such as quinoxalinones.

PLP-independent racemization: mechanistic and mutational studies of O-ureidoserine racemase (DcsC).

O-Ureidoserine racemase (DcsC) is a PLP-independent enzyme in the biosynthetic route to the antibiotic d-cycloserine. Here we present the recombinant expression and characterization of a significantly more active DcsC variant featuring an N-terminal SUMO-tag. Synthesis of enantiomeric pure inhibitors in combination with site-specific mutation of active site cysteines to serines of this enzyme offers closer insights into the mechanism of this transformation. Homology modelling with a close relative (diaminopimelate epimerase, DapF) inspired C- and N-terminal truncation of DcsC to produce a more compact yet still active enzyme variant.

Insights into the Mechanism of Action of the Two-Peptide Lantibiotic Lacticin 3147.

Lacticin 3147 is a two peptide lantibiotc (LtnA1 and LtnA2) that displays nanomolar activity against many Gram-positive bacteria. Lacticin 3147 may exert its antimicrobial effect by several mechanisms. Isothermal titration calorimetry experiments show that only LtnA1 binds to the peptidoglycan precursor lipid II, which could inhibit peptidoglycan biosynthesis. An experimentally supported model of the resulting complex suggests that the key binding partners are the C-terminus of LtnA1 and pyrophosphate of lipid II. A combination of in vivo and in vitro assays indicates that LtnA1 and LtnA2 can induce rapid membrane lysis without the need for lipid II binding. However, the presence of lipid II substantially increases the activity of lacticin 3147. Furthermore, studies with synthetic LtnA2 analogues containing either desmethyl- or oxa-lanthionine rings confirm that the precise geometry of these rings is essential for this synergistic activity.

Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases.

The apelin/apelin receptor system is widely distributed and has a dominant role in cardiovascular homeostasis and disease. The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is subsequently cleaved to generate a family of apelin peptides that possess similar functions but display different tissue distribution, potency and receptor binding affinity. Loss-of-function experiments using the apelin and the apelin receptor knockout mice and gain-of-function experiments using apelin peptides have delineated a well-defined role of the apelin axis in cardiovascular physiology and diseases. Activation of the apelin receptor by its cognate peptide ligand, apelin, induces a wide range of physiological effects, including vasodilation, increased myocardial contractility, angiogenesis, and balanced energy metabolism and fluid homeostasis. The apelin/apelin receptor pathway is also implicated in atherosclerosis, hypertension, coronary artery disease, heart failure, diabetes and obesity, making it a promising therapeutic target. Hence, research is expanding to develop novel therapies that inhibit degradation of endogenous apelin peptides or their analogues. Chemical synthesis of stable apelin receptor agonists aims to more efficiently enhance the activation of the apelin system. Targeting the apelin/apelin receptor axis has emerged as a novel therapeutic approach against cardiovascular diseases and an increased understanding of cardiovascular actions of the apelin system will help to develop effective interventions.

Lipopeptides from Bacillus and Paenibacillus spp.: A Gold Mine of Antibiotic Candidates.

The emergence of multidrug-resistant bacteria has placed a strain on health care systems and highlighted the need for new classes of antibiotics. Bacterial lipopeptides are secondary metabolites, generally produced by nonribosomal peptide synthetases that often exhibit broad-spectrum antimicrobial activity. Only two new structural types of antibiotics have entered the market in the last 40 years, linezolid and the bacterial lipopeptide daptomycin. A wide variety of bacteria produce lipopeptides, however Bacillus and Paenibacillus spp. in particular have yielded several potent antimicrobial lipopeptides. Many of the lipopeptides produced by these bacteria have been known for decades and represent a potential gold mine of antibiotic candidates. This list includes the polymyxins, octapeptins, polypeptins, iturins, surfactins, fengycins, fusaricidins, and tridecaptins, as well as some novel examples, including the kurstakins. These lipopeptides have a wide variety of activities, ranging from antibacterial and antifungal, to anticancer and antiviral. This review presents a reasonably comprehensive list of each class of lipopeptide and their known homologues. Emphasis has been placed on their antimicrobial activities, as well other potential applications for this interesting class of substances.