Nature's Combinatorial Biosynthesis Produces Vatiamides A–F

Moss, Nathan A.; Seiler, Grant; Leão, Tiago; Castro‐Falcón, Gabriel; Gerwick, Lena; Hughes, Chambers C.; Gerwick, William H.

doi:10.1002/anie.201902571

Cited by 39 publications

(42 citation statements)

References 36 publications

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“…For a second culture, Moorena sp. SIO1ASIH (collection code ASI16JUL142 CUL), which is the producer of a related suite of compounds produced by a unique and combinatorial biosynthetic logic (vatiamides A-F) [ 13 ], we complemented the short read sequencing with PacBio RS ® in order to reduce the draft genome to 24 contigs. Lastly, for a third culture, Leptolyngbya sp.…”

Section: Resultsmentioning

confidence: 99%

A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria

et al. 2021

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Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples.

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Section: Resultsmentioning

confidence: 99%

A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria

et al. 2021

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“…Compound 1 contains unusual structural features that, while having precedent in other cyanobacterial natural products, have not previously been seen together. Terminal alkynes can be found in several other natural products from Moorena spp., including jamaicamide B [ 66 ], carmabin A [ 71 ], and vatiamides A, C, and E [ 72 ], but having two is notable. While ribosomally synthesized and post-translationally modified peptides (RiPPs) and NRPS-derived natural products with amino acid subunits are common in cyanobacteria, lysine is not often seen, especially in the natural products of marine cyanobacteria [ 73 , 74 ].…”

Section: Resultsmentioning

confidence: 99%

Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii

et al. 2020

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The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA (Objective Relational Comparative Analysis) pipeline for flexible MS1 feature detection and multivariate analyses, were used to analyze various M. bouillonii samples. The observed chemogeographic patterns suggested the production of regionally specific natural products by M. bouillonii. Analyzing the drivers of these chemogeographic patterns allowed for the identification, targeted isolation, and structure elucidation of a regionally specific natural product, doscadenamide A (1). Analyses of MS2 fragmentation patterns further revealed this natural product to be part of an extensive family of herein annotated, proposed natural structural analogs (doscadenamides B–J, 2–10); the ensemble of structures reflect a combinatorial biosynthesis using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) components. Compound 1 displayed synergistic in vitro cancer cell cytotoxicity when administered with lipopolysaccharide (LPS). These discoveries illustrate the utility in leveraging chemogeographic patterns for prioritizing natural product discovery efforts.

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“…However, infrequently the tjh BGC could be responsible for the biosynthesis of two categories of compounds: rearranged tetracycline polyketides and glycosylated tetracyclines, likely owing to the abundant post‐modification enzymes involved in bifurcating the biosynthetic pathway. Very recently, rare cases of a single BGC governing the divergent biosynthesis of different categories of compounds have been observed in hybrid type I polyketide/non‐ribosomal peptide colibactins, vatiamides, and nucleoside pentostatin/arabinofuranosyladenine pathways . Thus, the discovery of tjh BGC‐directed biogeneration of two series of compounds provides the first example of divergent biosynthesis in the type II PKS system.…”

Section: Resultsmentioning

confidence: 99%

Activation and Characterization of Cryptic Gene Cluster: Two Series of Aromatic Polyketides Biosynthesized by Divergent Pathways

Ji¹,

Nie²,

Yin³

et al. 2019

Angewandte Chemie

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One biosynthetic gene cluster (BGC) usually governs the biosynthesis of a series of compounds exhibiting either the same or similar molecular scaffolds. Reported here is a multiplex activation strategy to awaken a cryptic BGC associated with tetracycline polyketides, resulting in the discovery of compounds having different core structures. By constitutively expressing a positive regulator gene in tandem mode, a single BGC directed the biosynthesis of eight aromatic polyketides with two types of frameworks, two pentacyclic isomers and six glycosylated tetracyclines. The proposed biosynthetic pathway, based on systematic gene inactivation and identification of intermediates, employs two sets of tailoring enzymes with a branching point from the same intermediate. These findings not only provide new insights into the role of tailoring enzymes in the diversification of polyketides, but also highlight a reliable strategy for genome mining of natural products.

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Nature's Combinatorial Biosynthesis Produces Vatiamides A–F

Abstract: Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Cited by 39 publications

References 36 publications

A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria

A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria

Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii

Activation and Characterization of Cryptic Gene Cluster: Two Series of Aromatic Polyketides Biosynthesized by Divergent Pathways

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