With progress in genome sequencing and data sharing, 1000s of bacterial genomes are publicly available. Genome mining – using bioinformatics tools in terms of biosynthetic gene cluster (BGC) identification, analysis and rating – has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing the genetic potential of the phylum Bacteroidetes revealed Chitinophaga as the most talented genus in terms of BGC abundance and diversity. Guided by the computational predictions, we conducted a metabolomics and bioactivity driven NP discovery program on 25 Chitinophaga strains. High numbers of peerless strain-specific metabolite buckets confirmed the upfront predicted biosynthetic potential and revealed a tremendous uncharted chemical space. Sourcing this dataset, we isolated the new iron chelating nonribosomally synthesized cyclic tetradeca- and pentadecalipodepsipeptide antibiotics chitinopeptins with activity against Candida, produced by C. eiseniae DSM 22224 and C. flava KCTC 62435, respectively.

Host plant specialization across herbivorous insects varies dramatically, but while the molecular mechanisms of host-plant adaptations are increasingly known, we often lack a comprehensive understanding of the selective forces that favor specialization. The milkweed bugs (Heteroptera: Lygaeinae) are engaged in ancestrally specialized associations with plants of the Apocynaceae from which they commonly sequester cardiac glycosides for defense, facilitated by resistant Na + /K + -ATPases and adaptations for transport, storage and discharge of toxins. Here, we show that three Lygaeinae species independently colonized four novel non-apocynaceous hosts that convergently produce cardiac glycosides. A fourth species shifted to a new source of toxins by tolerating and sequestering alkaloids from meadow saffron (Colchicum autumnale, Colchicaceae). Across three milkweed bug species tested, feeding on seeds containing toxins did not improve growth or speed of development, and even impaired growth and development in two species, but sequestration mediated protection of milkweed bugs against two natural predators: lacewing larvae and passerine birds. We conclude that physiological preadaptations and convergent phytochemistry facilitated novel specialized host associations. Since toxic seeds did not improve but either impaired growth or at most had neutral effects, selection by predators on sequestration of defenses, rather than the exploitation of additional profitable dietary resources, can lead to obligatory specialized host associations in otherwise generalist insects.

41Host plant specialization across herbivorous insects varies dramatically, but the underlying 42 evolutionary mechanisms are little-known. The milkweed bugs (Heteroptera: Lygaeinae) are 43 ancestrally associated with plants of the Apocynaceae from which they commonly sequester 44 cardiac glycosides for defense, facilitated by resistant Na + /K + -ATPases and adaptations for 45 transport, storage and discharge of toxins. Here, we show that three Lygaeinae species 46 independently colonized four novel non-apocynaceous hosts, convergently producing cardiac 47 glycosides. A fourth species shifted to a new source of toxins by tolerating and sequestering 48 alkaloids from meadow saffron (Colchicum autumnale, Colchicaceae). Across three species 49 tested, feeding on seeds containing toxins did not improve growth, but sequestration mediated 50 protection against predatory lacewing larvae and birds. We conclude that physiological 51 preadaptations and convergent phytochemistry facilitated novel specialized host associations. 52 Therefore, selection by predators on sequestration of defenses, rather than the exploitation of 53 novel dietary resources, can lead to obligatory specialized host associations in generalist insects.Herbivorous insects show tremendous variation with regard to dietary specialization. While it is a 84 long-standing assumption that phytochemicals may restrict and direct the evolution of host plant 85 use 1 , the explicit role of phytochemicals as drivers of host plant associations has been revealed in 86 only a few systems [2][3][4][5] . Proposed mechanisms of how plant secondary compounds could mediate 87 insect-plant interactions include physiological trade-offs in the efficiency of host plant use 88 between generalists and specialists 1,6-9 . Alternatively, it has been shown that novel host plant 89 associations can create enemy-free spaces for herbivores 10,11 either by providing defense 11 or 90 refuge from natural enemies 10 . However, even though it is widely recognized that many insects 91 not only use plants as a dietary resource but also sequester (i.e. absorb and store) plant toxins to 92 defend themselves against predators 12-14 , the extent to which sequestration could drive the 93 evolution of insect-host plant associations has rarely been addressed 4,15 . 94While it has been hypothesized that dietary specialization and sequestration of plant 95 toxins can lead to an evolutionary dead end 4,16 , there is evidence that ecological specialization 96 does not necessarily prevent host range expansion 4 . Nevertheless, sequestration and dietary 97 specialization seem to be evolutionarily linked 13,[17][18][19][20] , and predators driving the occupation of 98 enemy-free-spaces are typically considered to select for specialization 9,21 . Recent research 99 indicated that sequestration requires different resistance traits than are required to merely cope 100 with dietary toxins 22 , suggesting that selection by predators or parasitoids (i.e. the third trophic 101 level) opens a secon...

The development of pipelines for anti-infectives to be applied in plant, animal, and human health management are dried up. However, the resistance development against compounds in use calls for new lead structures.

High-throughput platforms facilitating screening campaigns of environmental samples are needed to discover new products of natural origin counteracting the spreading of antimicrobial resistances constantly threatening human and agricultural health. We applied a combination of droplet microfluidics and fluorescence-activated cell sorting (FACS)-based technologies to access and assess a microbial environmental sample. The cultivation performance of our microfluidics workflow was evaluated in respect to the utilized cultivation media by Illumina amplicon sequencing of a pool of millions of droplets, respectively. This enabled the rational selection of a growth medium supporting the isolation of microbial diversity from soil (five phyla affiliated to 57 genera) including a member of the acidobacterial subgroup 1 (genus Edaphobacter). In a second phase, the entire diversity covered by 1071 cultures was used for an arrayed bioprospecting campaign, resulting in > 6000 extracts tested against human pathogens and agricultural pests. After redundancy curation by using a combinatorial chemical and genomic fingerprinting approach, we assigned the causative agents present in the extracts. Utilizing UHPLC-QTOF-MS/ MS-guided fractionation and microplate-based screening assays in combination with molecular networking the production of bioactive ionophorous macrotetrolides, phospholipids, the cyclic lipopetides massetolides E, F, H and serratamolide A and many derivatives thereof was shown.