Recent progress in the structural study of ion channels as insecticide targets.

Ion channels, many expressed in insect neural and muscular systems, have drawn huge attention as primary targets of insecticides. With the recent technical breakthroughs in structural biology, especially in cryo-electron microscopy (cryo-EM), many new high-resolution structures of ion channel targets, apo or in complex with insecticides, have been solved, shedding light on the molecular mechanism of action of the insecticides and resistance mutations. These structures also provide accurate templates for structure-based insecticide screening and rational design. This review summarizes the recent progress in the structural studies of 5 ion channel families: the ryanodine receptor (RyR), the nicotinic acetylcholine receptor (nAChR), the voltage-gated sodium channel (VGSC), the transient receptor potential (TRP) channel, and the ligand-gated chloride channel (LGCC). We address the selectivity of the channel-targeting insecticides by examining the conservation of key coordinating residues revealed by the structures. The possible resistance mechanisms are proposed based on the locations of the identified resistance mutations on the 3D structures of the target channels and their impacts on the binding of insecticides. Finally, we discuss how to develop "green" insecticides with a novel mode of action based on these high-resolution structures to overcome the resistance.

The Roles of Optogenetics and Technology in Neurobiology: A Review.

Optogenetic is a technique that combines optics and genetics to control specific neurons. This technique usually uses adenoviruses that encode photosensitive protein. The adenovirus may concentrate in a specific neural region. By shining light on the target nerve region, the photosensitive protein encoded by the adenovirus is controlled. Photosensitive proteins controlled by light can selectively allow ions inside and outside the cell membrane to pass through, resulting in inhibition or activation effects. Due to the high precision and minimally invasive, optogenetics has achieved good results in many fields, especially in the field of neuron functions and neural circuits. Significant advances have also been made in the study of many clinical diseases. This review focuses on the research of optogenetics in the field of neurobiology. These include how to use optogenetics to control nerve cells, study neural circuits, and treat diseases by changing the state of neurons. We hoped that this review will give a comprehensive understanding of the progress of optogenetics in the field of neurobiology.

Ryanodine Receptor as Insecticide Target.

The ryanodine receptor (RyR) is one of the primary targets of commercial insecticides. The diamide insecticide family, including flubendiamide, chlorantraniliprole, cyantraniliprole, etc., targets insect RyRs and can be used to control a wide range of destructive agricultural pests. The diamide insecticides are highly selective against lepidopteran and coleopteran pests with relatively low toxicity for non-target species, such as mammals, fishes, and beneficial insects. However, recently mutations identified on insect RyRs have emerged and caused resistance in several major agricultural pests throughout different continents. This review paper summarizes the recent findings on the structure and function of insect RyRs as insecticide targets. Specifically, we examine the structures of RyRs from target and non-target species, which reveals the molecular basis for insecticide action and selectivity. We also examine the structural and functional changes of RyR caused by the resistance mutations. Finally, we examine the progress in RyR structure-based insecticide design and discuss how this might help the development of a new generation of green insecticides.

Overcoming physical stromal barriers to cancer immunotherapy.

Immunotherapy has emerged as an unprecedented hope for the treatment of notoriously refractory cancers. Numerous investigational drugs and immunotherapy-including combination regimens are under preclinical and clinical investigation. However, only a small patient subpopulation across different types of cancer responds to the therapy due to the presence of several mechanisms of resistance. There have been extensive efforts to overcome this limitation and to expand the patient population that could be benefited by this state-of-the-art therapeutic modality. Among various causes of the resistance, we here focus on physical stromal barriers that impede the access of immunotherapeutic drug molecules and/or native and engineered immune cells to cancer tissues and cells. Two primary stromal barriers that contribute to the resistance include aberrant tumor vasculatures and excessive extracellular matrix build-ups that restrict extravasation and infiltration, respectively, of molecular and cellular immunotherapeutic agents into tumor tissues. Here, we review the features of these barriers that limit the efficacy of immunotherapy and discuss recent advances that could potentially help immunotherapy overcome the barriers and improve therapeutic outcomes.

Different carbon and nitrogen sources regulated docosahexaenoic acid (DHA) production of Thraustochytriidae sp. PKU#SW8 through a fully functional polyunsaturated fatty acid (PUFA) synthase gene (pfaB).

Docosahexaenoic acid (DHA, C22:6) production in thraustochytrids is known to be mediated independently through polyunsaturated fatty acid (PUFA) synthase and fatty acid synthase systems. This study elucidates the unresolved effects of different carbon and nitrogen sources on the functionality of PUFA synthase subunit B (pfaB) and corresponding DHA production in Thraustochytriidae sp. PKU#SW8. Carbon and nitrogen sources showed significant effect on the pfaB gene expression and DHA production patterns, but these patterns did not correspond with each other, suggesting the strong role of substrates in differential induction of the two synthase systems. Nitrogen starvation increased DHA yield in parallel with upregulated gene expression, showing strong indication of PUFA synthase activity in N-deficient culture. The fully functional catalytic activity of PfaB subunit from strain PKU#SW8 in a heterologous host was also demonstrated. This study provides the direct evidence of pfaB gene actively for DHA biosynthesis in Thraustochytriidae sp. PKU#SW8.

Fed-batch fermentation of mixed carbon source significantly enhances the production of docosahexaenoic acid in Thraustochytriidae sp. PKU#Mn16 by differentially regulating fatty acids biosynthetic pathways.

This study reports comparative evaluation of the growth and DHA productivity of the thraustochytrid strain Thraustochytriidae PKU#Mn16 fermented with seven different substrate feeding strategies. Of these strategies, fed-batch fermentation of the mixed substrate (glucose & glycerol) yielded the maximum growth (52.2 ±â€¯1.5 g/L), DHA yield (Yp/s: 8.65) and productivity (100.7 ±â€¯2.9 mg/L-h), comparable with those of previously reported Aurantiochytrium strains. Transcriptomics analyses revealed that glucose upregulated some genes of the fatty acid synthase pathway whereas glycerol upregulated a few genes of the polyketide synthase pathway. Co-fermentation of the mixed substrate differentially regulated genes of these two pathways and significantly enhanced the DHA productivity. Furthermore, some genes involved in DNA replication, phagosome, carbon metabolism, and ß-oxidation were also found to alter significantly during the mixed-substrate fermentation. Overall, this study provides a unique strategy for enhancing growth and DHA productivity of the strain PKU#Mn16 and the first insight into the mechanisms underlying mixed-substrate fermentation.

Impact of environmental gradients on the abundance and diversity of planktonic fungi across coastal habitats of contrasting trophic status.

Fungal communities in the coastal waters have long been known to be dynamic with a significant role in organic matter cycling. However, the effects of environmental gradients on their community structures are poorly described. Here we studied three coastal sites off the South China Sea, namely Pearl River Estuary (PE), Shenzhen Bay (SB), and Daya Bay (DB) with contrasting trophic status and heterogenous local influences. Environmental analysis of these sites suggested higher nutrient and low salinity levels at PE and SB with wide variability compared to DB. Average molecular abundances (18S rRNA gene copy numbers) at sites PE (1.05 ±â€¯0.27 × 107 copies L-1) and SB (1.2 ±â€¯0.69 × 107 copies L-1) were similar and significantly higher (P < 0.05) than that at site DB (5.5 ±â€¯9.5 × 105 copies L-1). Although planktonic fungi were molecularly abundant at the three sites, live fungal biomass based on ergosterol assay was detected only at some stations of PE and SB. Both molecular abundance and live biomass were significantly correlated with chemical oxygen demand, nutrients, and phytoplankton biomass, supporting their role in detritus turnover. The fungal communities were unprecedently diverse with the ubiquitous dominance of Dikarya and the occasional predominance of Glomeromycota, Mucoromycota, Mortierellomycota, and Chytridiomycota. A total of 24 classes, 46 orders, 71 families, 59 genera, and eight species were classified within the eight detected phyla, including the new finding of ascomycetous class Geoglossomycetes in coastal waters. Salinity and nitrate were the significant (r2 = 0.70, P < 0.05) factors that determined the ß-diversity of fungal communities. Overall, this study suggests that although planktonic fungi are ubiquitous in coastal habitats, their molecular abundances and diversities (both α and ß) are significantly determined by environmental gradients, particularly the salinity, COD and nitrate levels of coastal waters.

Culturable Diversity and Lipid Production Profile of Labyrinthulomycete Protists Isolated from Coastal Mangrove Habitats of China.

Labyrinthulomycete protists have gained significant attention in the recent past for their biotechnological importance. Yet, their lipid profiles are poorly described because only a few large-scale isolation attempts have been made so far. Here, we isolated more than 200 strains from mangrove habitats of China and characterized the molecular phylogeny and lipid accumulation potential of 71 strains. These strains were the closest relatives of six genera namely Aurantiochytrium, Botryochytrium, Parietichytrium, Schizochytrium, Thraustochytrium, and Labyrinthula. Docosahexaenoic acid (DHA) production of the top 15 strains ranged from 0.23 g/L to 1.14 g/L. Two labyrinthulid strains, GXBH-107 and GXBH-215, exhibited unprecedented high DHA production potential with content >10% of biomass. Among all strains, ZJWZ-7, identified as an Aurantiochytrium strain, exhibited the highest DHA production. Further optimization of culture conditions for strain ZJWZ-7 showed improved lipid production (1.66 g/L DHA and 1.68 g/L saturated fatty acids (SFAs)) with glycerol-malic-acid, peptone-yeast-extract, initial pH 7, 28 °C, and rotation rate 150 rpm. Besides, nitrogen source, initial pH, temperature, and rotation rate had significant effects on the cell biomass, DHA, and SFAs production. This study provides the identification and characterization of nearly six dozen thraustochytrids and labyrinthulids with high potential for lipid accumulation.

Gradients of three coastal environments off the South China Sea and their impacts on the dynamics of heterotrophic microbial communities.

Heterotrophic fungus-like marine protists are recognized to contribute significantly to the coastal carbon cycling largely due to their high biomass and ability to decompose recalcitrant organic matter. Yet, little is known about their dynamics at polluted coastal environments in the context of heterotrophic microbial communities. Here, we present the dynamics of these protists relative to their heterotrophic counterparts in three different environments, namely Pearl River Estuary (ZJK), Shenzhen Bay (SZW) and Daya Bay (DYW) along the coastline of South China Sea. ZJK and SZW were characterized by low salinity and high N levels with large variations, unlike DYW. However, the average abundance of fungus-like protists did not differ significantly (P > 0.05) among these environments, except that it increased in August (422 ±â€¯264 cells/mL, P < 0.01) over March, May and October. Correlation analysis revealed association of their abundance to different environmental factors, namely dissolved organic N in ZJK (rho = -0.87); NH4+ (rho = 0.64) and Chl a (rho = 0.73) in SZW; and salinity (rho = 0.46), DO (rho = 0.57) and total P (rho = 0.48) in DYW, suggesting distinct influence of trophic conditions. Analysis of their abundance relative to other heterotrophic protists (HP) shows that fungus-like protists display selective advantage over HP in the environment (DWY) with low N levels. Further, the similar biomass fraction (ZJK: 5.97 ±â€¯6.23%, SZW: 5.97 ±â€¯5.28%, and DYW: 12.1 ±â€¯11.4%; P > 0.05) of fungus-like protists relative to heterotrophic bacteria, suggest their invariable contribution to carbon cycling. Thus, dynamics of fungus-like protists in relation to their heterotrophic counterparts is largely regulated by the trophic conditions of coastal environments.

Bio-based squalene production by Aurantiochytrium sp. through optimization of culture conditions, and elucidation of the putative biosynthetic pathway genes.

Newly-isolated thraustochytrid strains from coastal waters of China were characterized as bioresource of squalene and the culture condition for the top producer was systematically optimized. Phylogenetic analysis revealed that eight squalene-producing isolates were closely related to genus Aurantiochytrium and one to genus Labyrinthula. The top producer, Aurantiochytrium sp. TWZ-97, produced squalene up to 188.6 mg/L at 28 °C in a 5-L bioreactor containing optimal medium (glucose: 40 g/L, monosodium glutamate: 3 g/L, yeast extract: 25 g/L, and NaCl: 6 g/L), which was 6-fold higher than that under unoptimized condition. Transcriptome analysis revealed for the first time the presence of seven key genes of mevalonate pathway for squalene biosynthesis in strain TWZ-97. Medium optimization yielded a 2.23-fold higher expression of the squalene synthase gene under optimal condition compared to unoptimized. This study provides a potential thraustochytrid strain TWZ-97 as bioresource of squalene and uncovers novel information about its squalene biosynthesis pathway for future strain improvement.

Molecular Detection and Spatiotemporal Characterization of Labyrinthulomycete Protist Diversity in the Coastal Waters Along the Pearl River Delta.

The heterotrophic labyrinthulomycete protists have long been known to play an important role in the nutrient cycling of coastal seawater. Yet, their spatiotemporal abundance and diversity in polluted coastal waters remain poorly discussed, due in part to the paucity of a rapid detection method. To this end, we developed a qPCR detection method based on a newly designed primer pair targeting their 18S rRNA gene. Using this method, we studied the population dynamics of labyrinthulomycete protists in nutrient-rich (Shenzhen Bay) and low-nutrient (Daya) coastal habitats along the Pearl River Delta. We found a significantly (P < 0.05) higher abundance of Labyrinthulomycetes in the Shenzhen bay (average 3455 gene copies mL-1) than that in Daya Bay (average 378 gene copies mL-1). Their abundance gradient positively correlated (P < 0.05) with the levels of inorganic nitrogen and phosphates. Further characterization of the molecular diversity of these protists in Shenzhen Bay using different primer sets revealed the presence of several genera besides a large number of unclassified OTUs. Regardless of the primer biases, our results show significant (P < 0.05) spatiotemporal changes in the molecular abundance and diversity of these heterotrophic protists. Overall, this study provides a rapid molecular detection tool for Labyrinthulomycetes and expands our current understanding of their dynamics controlled by physicochemical gradients in coastal waters.

Comparative analysis reveals unexpected genome features of newly isolated Thraustochytrids strains: on ecological function and PUFAs biosynthesis.

BACKGROUND: Thraustochytrids are unicellular fungal-like marine protists with ubiquitous existence in marine environments. They are well-known for their ability to produce high-valued omega-3 polyunsaturated fatty acids (ω-3-PUFAs) (e.g., docosahexaenoic acid (DHA)) and hydrolytic enzymes. Thraustochytrid biomass has been estimated to surpass that of bacterioplankton in both coastal and oceanic waters indicating they have an important role in microbial food-web. Nevertheless, the molecular pathway and regulatory network for PUFAs production and the molecular mechanisms underlying ecological functions of thraustochytrids remain largely unknown. RESULTS: The genomes of two thraustochytrids strains (Mn4 and SW8) with ability to produce DHA were sequenced and assembled with a hybrid sequencing approach utilizing Illumina short paired-end reads and Pacific Biosciences long reads to generate a highly accurate genome assembly. Phylogenomic and comparative genomic analyses found that DHA-producing thraustochytrid strains were highly similar and possessed similar gene content. Analysis of the conventional fatty acid synthesis (FAS) and the polyketide synthase (PKS) systems for PUFAs production only detected incomplete and fragmentary pathways in the genome of these two strains. Surprisingly, secreted carbohydrate active enzymes (CAZymes) were found to be significantly depleted in the genomes of these 2 strains as compared to other sequenced relatives. Furthermore, these two strains possess an expanded gene repertoire for signal transduction and self-propelled movement, which could be important for their adaptations to dynamic marine environments. CONCLUSIONS: Our results demonstrate the possibility of a third PUFAs synthesis pathway besides previously described FAS and PKS pathways encoded in the genome of these two thraustochytrid strains. Moreover, lack of a complete set of hydrolytic enzymatic machinery for degrading plant-derived organic materials suggests that these two DHA-producing strains play an important role as a nutritional source rather than a nutrient-producer in marine microbial-food web. Results of this study suggest the existence of two types of saprobic thraustochytrids in the world's ocean. The first group, which does not produce cellulosic enzymes and live as 'left-over' scavenger of bacterioplankton, serves as a dietary source for the plankton of higher trophic levels and the other possesses capacity to live on detrital organic matters in the marine ecosystems.

Improved production of docosahexaenoic acid in batch fermentation by newly-isolated strains of Schizochytrium sp. and Thraustochytriidae sp. through bioprocess optimization.

Thraustochytrids, rich in docosahexaenoic acid (DHA, C22:6ω3), represent a potential source of dietary fatty acids. Yet, the effect of culture conditions on growth and fatty acid composition vary widely among different thraustochytrid strains. Two different thraustochytrid strains, Schizochytrium sp. PKU#Mn4 and Thraustochytriidae sp. PKU#Mn16 were studied for their growth and DHA production characteristics under various culture conditions. Although they exhibited similar fatty acid profiles, PKU#Mn4 seemed a good candidate for industrial DHA fermentation while PKU#Mn16 displayed growth tolerance to a wide range of process conditions. Relative DHA content of 48.5% and 49.2% (relative to total fatty acids), respectively, were achieved on glycerol under their optimal flask culture conditions. Maximum DHA yield (Yp/x) of 21.0% and 18.9% and productivity of 27.6 mg/L-h and 31.9 mg/L-h were obtained, respectively, in 5-L bioreactor fermentation operated with optimal conditions and dual oxygen control strategy. A 3.4- and 2.8-fold improvement of DHA production (g/L), respectively, was achieved in this study. Overall, our study provides the potential of two thraustochytrid strains and their culture conditions for efficient production of DHA-rich oil.

Alleviation of reactive oxygen species enhances PUFA accumulation in Schizochytrium sp. through regulating genes involved in lipid metabolism.

The unicellular heterotrophic thraustochytrids are attractive candidates for commercial polyunsaturated fatty acids (PUFA) production. However, the reactive oxygen species (ROS) generated in their aerobic fermentation process often limits their PUFA titer. Yet, the specific mechanisms of ROS involvement in the crosstalk between oxidative stress and intracellular lipid synthesis remain poorly described. Metabolic engineering to improve the PUFA yield in thraustochytrids without compromising growth is an important aspect of economic feasibility. To fill this gap, we overexpressed the antioxidative gene superoxide dismutase (SOD1) by integrating it into the genome of thraustochytrid Schizochytrium sp. PKU#Mn4 using a novel genetic transformation system. This study reports the ROS alleviation, enhanced PUFA production and transcriptome changes resulting from the SOD1 overexpression. SOD1 activity in the recombinant improved by 5.2-71.6% along with 7.8-38.5% decline in ROS during the fermentation process. Interestingly, the total antioxidant capacity in the recombinant remained higher than wild-type and above zero in the entire process. Although lipid profile was similar to that of wild-type, the concentrations of major fatty acids in the recombinant were significantly (p ≤ 0.05) higher. The PUFA titer increased up to 1232 ±â€¯41 mg/L, which was 32.9% higher (p ≤ 0.001) than the wild type. Transcriptome analysis revealed strong downregulation of genes potentially involved in ß-oxidation of fatty acids in peroxisome and upregulation of genes catalyzing lipid biosynthesis. Our results enrich the knowledge on stress-induced PUFA biosynthesis and the putative role of ROS in the regulation of lipid metabolism in oleaginous thraustochytrids. This study provides a new and alternate strategy for cost-effective industrial fermentation of PUFA.

Enhanced saturated fatty acids accumulation in cultures of newly-isolated strains of Schizochytrium sp. and Thraustochytriidae sp. for large-scale biodiesel production.

Heterotrophic marine protists (Thraustochytrids) have received increasingly global attention as a renewable, sustainable and alternative source of biodiesel because of their high ability of saturated fatty acids (SFAs) accumulation. Yet, the influence of extrinsic factors (nutrients and environmental conditions) on thraustochytrid culture and optimal conditions for high SFAs production are poorly described. In the present study, two different thraustochytrid strains, Schizochytrium sp. PKU#Mn4 and Thraustochytriidae sp. PKU#Mn16 were studied for their growth and SFAs production profiles under various conditions (carbon, nitrogen, temperature, pH, KH2PO4, salinity, and agitation speed). Of the culture conditions, substrates (C and N) source and conc., temperature, and agitation speed significantly influenced the cell growth and SFAs production of both strains. Although both the strains were capable of growth and SFAs production in the broad range of culture conditions, their physiological responses to KH2PO4, pH, and salinity were dissimilar. Under their optimal batch culture conditions, peak SFAs productions of 3.3g/L and 2.2g/L with 62% and 49% SFAs contents (relative to total fatty acids) were achieved, respectively. The results of 5-L fed-batch fermentation under optimal conditions showed a nearly 4.5-fold increase in SFAs production (i.e., 7.5g/L) by both strains compared to unoptimized conditions. Of the two strains, the quality of biodiesel produced from the fatty acids of PKU#Mn4 met the biodiesel standard defined by ASTM6751. This study, to the knowledge of the authors, is the first comprehensive report of optimal fermentation conditions demonstrating enhanced SFAs production by strains belonging to two different thraustochytrid genera and provides the basis for large-scale biodiesel production.

Mining terpenoids production and biosynthetic pathway in thraustochytrids.

Terpenoids are major bioactive compounds produced by microalgae and other eukaryotic microorganisms. Mining metabolic potential of marine microalgae for commercial production of terpenoids suggest thraustochytrids as one of the promising cell factories. The identification of potential thraustochytrid strains and relevant laboratory scale bioprocesses has been pursued largely. Further investigations in the improvement of terpenoids biosynthesis expect relevant molecular mechanisms to be understood directing metabolic engineering of the pathways. In this review, fermentative and mechanistic studies to identify key enzymes and pathways that are associated to terpenoids biosynthesis in thraustochytrids are discussed. Exploration of biosynthesis mechanisms in other model organisms facilitated identification of potential molecular targets for engineering terpenoids biosynthetic pathway in thraustochytrids. In addition, the preliminary genetic manipulation and in silico analysis in this review provides a platform for system-level metabolic engineering towards thraustochytrid strains improvement. Overall, the review contributes comprehensive information to allow better terpenoids productivity in thraustochytrids.

Toward a better guard of coastal water safety-Microbial distribution in coastal water and their facile detection.

Prosperous development in marine-based tourism has raised increasing concerns over the sanitary quality of coastal waters with potential microbial contamination. The World Health Organization has set stringent standards over a list of pathogenic microorganisms posing potential threats to people with frequent coastal water exposure and has asked for efficient detection procedures for pathogen facile identification. Inspection of survey events regarding the occurrence of marine pathogens in recreational beaches in recent years has reinforced the need for the development of a rapid identification procedure. In this review, we examine the possibility of recruiting uniform molecular assays to identify different marine pathogens and the feasibility of appropriate biomarkers, including enterochelin biosynthetic genes, for general toxicity assays. The focus is not only on bacterial pathogens but also on other groups of infectious pathogens. The ultimate goal is the development of a handy method to more efficiently and rapidly detect marine pathogens.

Mechanisms of fatty acid synthesis in marine fungus-like protists.

Thraustochytrids are unicellular fungus-like protists and are well known for their ability to produce interesting nutraceutical compounds. Significant efforts have been made to improve their efficient production of important fatty acids (FAs), mostly by optimizing fermentation conditions and selecting highly productive thraustochytrid strains. Furthermore, noticeable improvements have been made in understanding the mechanism of FA biosynthesis, allowing for a better understanding of how thraustochytrids assemble these unique metabolites and how their biosynthesis is coupled with other related pathways. This review summarizes recent achievements on two major FA biosynthesis pathways, the standard pathway and the polyketide synthase pathway, and detail features of individual enzymes involved in FA biosynthesis, biotechnological advances in pathway engineering and enzyme characterization, and the discovery of other pathways that affect the efficiency of FA accumulation. Perspectives of biotechnological potential application of thraustochytrids are also discussed.

Iterative assembly of two separate polyketide chains by the same single-module bacterial polyketide synthase in the biosynthesis of HSAF.

Antifungal HSAF (heat-stable antifungal factor, dihydromaltophilin) is a polycyclic tetramate macrolactam from the biocontrol agent Lysobacter enzymogenes. Its biosynthetic gene cluster contains only a single-module polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS), although two separate hexaketide chains are required to assemble the skeleton. To address the unusual biosynthetic mechanism, we expressed the biosynthetic genes in two "clean" strains of Streptomyces and showed the production of HSAF analogues and a polyene tetramate intermediate. We then expressed the PKS module in Escherichia coli and purified the enzyme. Upon incubation of the enzyme with acyl-coenzyme A and reduced nicotinamide adenine dinucleotide phosphate (NADPH), a polyene was detected in the tryptic acyl carrier protein (ACP). Finally, we incubated the polyene-PKS with the NRPS module in the presence of ornithine and adenosine triphosphate (ATP), and we detected the same polyene tetramate as that in Streptomyces transformed with the PKS-NRPS alone. Together, our results provide evidence for an unusual iterative biosynthetic mechanism for bacterial polyketide-peptide natural products.

Bioactive natural products from Lysobacter.

The gliding Gram-negative Lysobacter bacteria are emerging as a promising source of new bioactive natural products. These ubiquitous freshwater and soil microorganisms are fast growing, simple to use and maintain, and genetically amenable for biosynthetic engineering. This Highlight reviews a group of biologically active and structurally distinct natural products from the genus Lysobacter, with a focus on their biosyntheses. Although Lysobacter sp. are known as prolific producers of bioactive natural products, detailed molecular mechanistic studies of their enzymatic assembly have been surprisingly scarce. We hope to provide a snapshot of the important work done on the lysobacterial natural products and to provide useful information for future biosynthetic engineering of novel antibiotics in Lysobacter.