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A Widely Distributed Biosynthetic Cassette Is Responsible for Diverse Plant Side Chain Cross-Linked Cyclopeptides.

ABSTRACT: Cyclopeptide alkaloids are an abundant class of plant cyclopeptides with over 200 analogs described and bioactivities ranging from analgesic to antiviral. While these natural products have been known for decades, their biosynthetic basis remains unclear. Using a transcriptome-mining approach, we link the cyclopeptide alkaloids from Ceanothus americanus to dedicated RiPP precursor peptides and identify new, widely distributed split BURP peptide cyclase containing gene clusters. Guided by our bioinformatic analysis, we identify and isolate new cyclopeptides from Coffea arabica, which we named arabipeptins. Reconstitution of the enzyme activity for the BURP found in the biosynthesis of arabipeptin A validates the activity of the newly discovered split BURP peptide cyclases. These results expand our understanding of the biosynthetic pathways responsible for diverse cyclic plant peptides and suggest that these side chain cross-link modifications are widely distributed in eudicots.

SUBMITTER: Lima ST

PROVIDER: S-EPMC10107690 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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A Widely Distributed Biosynthetic Cassette Is Responsible for Diverse Plant Side Chain Cross-Linked Cyclopeptides.

Lima Stella T ST Ampolini Brigitte G BG Underwood Ethan B EB Graf Tyler N TN Earp Cody E CE Khedi Imani C IC Pasquale Michael A MA Chekan Jonathan R JR

Angewandte Chemie (International ed. in English) 20230112 7

Cyclopeptide alkaloids are an abundant class of plant cyclopeptides with over 200 analogs described and bioactivities ranging from analgesic to antiviral. While these natural products have been known for decades, their biosynthetic basis remains unclear. Using a transcriptome-mining approach, we link the cyclopeptide alkaloids from Ceanothus americanus to dedicated RiPP precursor peptides and identify new, widely distributed split BURP peptide cyclase containing gene clusters. Guided by our bioi ...[more]

PMID: 36529706

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Project description:BackgroundRecently, a gene cluster responsible for biosynthesis of ustiloxin in Aspergillus flavus was identified as the first case of a ribosomally synthesized and post-translationally modified peptide (RiPP) synthetic pathway in Ascomycota. RiPPs are biosynthesized from precursor peptides, which are processed to produce the RiPP backbone (core peptides) for further modifications such as methylation and cyclization. Ustiloxin precursor peptide has two distinctive features: a signal peptide for translocation into the endoplasmic reticulum and highly repeated core sequences cleaved by Kex2 protease in the Golgi apparatus. On the basis of these characteristics, the ustiloxin-type RiPP precursor peptides or Kex2-processed repeat proteins (KEPs) in strains belonging to the Fungi kingdom were computationally surveyed, in order to investigate the distribution and putative functions of KEPs in fungal ecology.ResultsIn total, 7878 KEPs were detected in 1345 of 1461 strains belonging to 8 phyla. The average number of KEPs per strain was 5.25 in Ascomycota and 5.30 in Basidiomycota, but only 1.35 in the class Saccharomycetes (Ascomycota) and 1.00 in the class Tremellomycetes (Basidiomycota). The KEPs were classified into 838 types and 2560 stand-alone ones, which had no homologs. Nearly 200 types were distributed in more than one genus, and 14 types in more than one phylum. These types included yeast α-mating factors and fungal pheromones. Genes for 22% KEPs were accompanied by genes for DUF3328-domain-containing proteins, which are indispensable for cyclization of the core peptides. DUF3328-domain-containing protein genes were located at an average distance of 3.09 genes from KEP genes. Genes for almost all (with three exceptions) KEPs annotated as yeast α-mating factors or fungal pheromones were not accompanied by DUF3328-domain-containing protein genes.ConclusionKEPs are widely distributed in the Fungi kingdom, but their repeated sequences are highly diverse. From these results and some examples, a hypothesis was raised that KEPs initially evolved as unmodified linear peptides (e.g., mating factors), and then those that adopted a modified cyclic form emerged (e.g., toxins) to utilize their strong bioactivity against predators and competitive microorganisms.

Project description:Desulfatiglans-related organisms comprise one of the most abundant deltaproteobacterial lineages in marine sediments where they occur throughout the sediment column in a gradient of increasing sulfate and organic carbon limitation with depth. Characterized Desulfatiglans isolates are dissimilatory sulfate reducers able to grow by degrading aromatic hydrocarbons. The ecophysiology of environmental Desulfatiglans-populations is poorly understood, however, possibly utilization of aromatic compounds may explain their predominance in marine subsurface sediments. We sequenced and analyzed seven Desulfatiglans-related single-cell genomes (SAGs) from Aarhus Bay sediments to characterize their metabolic potential with regard to aromatic compound degradation and energy metabolism. The average genome assembly size was 1.3 Mbp and completeness estimates ranged between 20 and 50%. Five of the SAGs (group 1) originated from the sulfate-rich surface part of the sediment while two (group 2) originated from sulfate-depleted subsurface sediment. Based on 16S rRNA gene amplicon sequencing group 2 SAGs represent the more frequent types of Desulfatiglans-populations in Aarhus Bay sediments. Genes indicative of aromatic compound degradation could be identified in both groups, but the two groups were metabolically distinct with regard to energy conservation. Group 1 SAGs carry a full set of genes for dissimilatory sulfate reduction, whereas the group 2 SAGs lacked any genetic evidence for sulfate reduction. The latter may be due to incompleteness of the SAGs, but as alternative energy metabolisms group 2 SAGs carry the genetic potential for growth by acetogenesis and fermentation. Group 1 SAGs encoded reductive dehalogenase genes, allowing them to access organohalides and possibly conserve energy by their reduction. Both groups possess sulfatases unlike their cultured relatives allowing them to utilize sulfate esters as source of organic carbon and sulfate. In conclusion, the uncultivated marine Desulfatiglans populations are metabolically diverse, likely reflecting different strategies for coping with energy and sulfate limitation in the subsurface seabed.

Dataset Information

A Widely Distributed Biosynthetic Cassette Is Responsible for Diverse Plant Side Chain Cross-Linked Cyclopeptides.

Publications

A Widely Distributed Biosynthetic Cassette Is Responsible for Diverse Plant Side Chain Cross-Linked Cyclopeptides.

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