Dataset Information

Drivers of metabolic diversification: how dynamic genomic neighbourhoods generate new biosynthetic pathways in the Brassicaceae.

ABSTRACT: Plants produce an array of specialized metabolites with important ecological functions. The mechanisms underpinning the evolution of new biosynthetic pathways are not well-understood. Here, we exploit available genome sequence resources to investigate triterpene biosynthesis across the Brassicaceae. Oxidosqualene cyclases (OSCs) catalyze the first committed step in triterpene biosynthesis. Systematic analysis of 13 sequenced Brassicaceae genomes was performed to identify all OSC genes. The genome neighbourhoods (GNs) around a total of 163 OSC genes were investigated to identify Pfam domains significantly enriched in these regions. All-vs-all comparisons of OSC neighbourhoods and phylogenomic analysis were used to investigate the sequence similarity and evolutionary relationships of the numerous candidate triterpene biosynthetic gene clusters (BGCs) observed. Functional analysis of three representative BGCs was carried out and their triterpene pathway products were elucidated. Our results indicate that plant genomes are remarkably plastic, and that dynamic GNs generate new biosynthetic pathways in different Brassicaceae lineages by shuffling the genes encoding a core palette of triterpene-diversifying enzymes, presumably in response to strong environmental selection pressure. These results illuminate a genomic basis for diversification of plant-specialized metabolism through natural combinatorics of enzyme families, which can be mimicked using synthetic biology to engineer diverse bioactive molecules.

SUBMITTER: Liu Z

PROVIDER: S-EPMC7383575 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Drivers of metabolic diversification: how dynamic genomic neighbourhoods generate new biosynthetic pathways in the Brassicaceae.

Liu Zhenhua Z Suarez Duran Hernando G HG Harnvanichvech Yosapol Y Stephenson Michael J MJ Schranz M Eric ME Nelson David D Medema Marnix H MH Osbourn Anne A

The New phytologist 20191228 4

Plants produce an array of specialized metabolites with important ecological functions. The mechanisms underpinning the evolution of new biosynthetic pathways are not well-understood. Here, we exploit available genome sequence resources to investigate triterpene biosynthesis across the Brassicaceae. Oxidosqualene cyclases (OSCs) catalyze the first committed step in triterpene biosynthesis. Systematic analysis of 13 sequenced Brassicaceae genomes was performed to identify all OSC genes. The genom ...[more]

PMID: 31769874

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Project description:BackgroundA wide range of bioactive compounds is produced by enzymes and enzymatic complexes encoded in biosynthetic gene clusters (BGCs). These BGCs can be identified and functionally annotated based on their DNA sequence. Candidates for further research and development may be prioritized based on properties such as their functional annotation, (dis)similarity to known BGCs, and bioactivity assays. Production of the target compound in the native strain is often not achievable, rendering heterologous expression in an optimized host strain as a promising alternative. Genome-scale metabolic models are frequently used to guide strain development, but large-scale incorporation and testing of heterologous production of complex natural products in this framework is hampered by the amount of manual work required to translate annotated BGCs to metabolic pathways. To this end, we have developed a pipeline for an automated reconstruction of BGC associated metabolic pathways responsible for the synthesis of non-ribosomal peptides and polyketides, two of the dominant classes of bioactive compounds.ResultsThe developed pipeline correctly predicts 72.8% of the metabolic reactions in a detailed evaluation of 8 different BGCs comprising 228 functional domains. By introducing the reconstructed pathways into a genome-scale metabolic model we demonstrate that this level of accuracy is sufficient to make reliable in silico predictions with respect to production rate and gene knockout targets. Furthermore, we apply the pipeline to a large BGC database and reconstruct 943 metabolic pathways. We identify 17 enzymatic reactions using high-throughput assessment of potential knockout targets for increasing the production of any of the associated compounds. However, the targets only provide a relative increase of up to 6% compared to wild-type production rates.ConclusionWith this pipeline we pave the way for an extended use of genome-scale metabolic models in strain design of heterologous expression hosts. In this context, we identified generic knockout targets for the increased production of heterologous compounds. However, as the predicted increase is minor for any of the single-reaction knockout targets, these results indicate that more sophisticated strain-engineering strategies are necessary for the development of efficient BGC expression hosts.

Project description:Plants emit characteristic organic volatile compounds (VOCs) with diverse biological/ecological functions. However, the links between plant species/varieties and their phytochemical emission profiles remain elusive. Here, we developed a direct headspace solid-phase microextraction (HS-SPME) technique and combined with non-targeted gas chromatography?high-resolution mass spectrometry (GC-HRMS) platform to investigate the VOCs profiles of 12 common Brassicaceae vegetables (watercress, rocket, Brussels sprouts, broccoli, kai lan, choy sum, pak choi, cabbage, Chinese cabbage, cauliflower, radish and cherry radish). The direct HS-SPME sampling approach enabled reproducible capture of the rapid-emitting VOCs upon plant tissue disruption. The results revealed extensive variation in VOCs profiles among the 12 Brassicaceae vegetables. Furthermore, principal component analysis (PCA) showed that the VOC profiles could clearly distinguish the 12 Brassicaceae vegetables, and that these profiles well reflected the classical morphological classification. After multivariate statistical analysis, 44 VOCs with significant differences among the Brassicaceae vegetables were identified. Pathway analysis showed that three secondary metabolism pathways, including the fatty acid pathway, methylerythritol phosphate (MEP) pathway and glucosinolate (GLS) pathway, behave distinctively in these vegetables. These three pathways are responsible for the generation and emission of green leaf volatiles (GLVs), terpenes and isothiocyanates (ITCs), respectively. Correlation analysis further showed that volatile metabolites formed via the common pathway had significantly positive correlations, whereas metabolites from different pathways had either non-significant or significantly negative correlations. Genetic influences on these metabolites across various vegetable types were also evaluated. These findings extend our phytochemical knowledge of the 12 edible Brassicaceae vegetables and provide useful information on their secondary metabolism.

Dataset Information

Drivers of metabolic diversification: how dynamic genomic neighbourhoods generate new biosynthetic pathways in the Brassicaceae.

Publications

Drivers of metabolic diversification: how dynamic genomic neighbourhoods generate new biosynthetic pathways in the Brassicaceae.

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