Polyketide β-branching: diversity, mechanism and selectivity

Walker, Paul D.; Weir, Angus N. M.; Willis, Christine L.; Crump, Matthew P.

doi:10.1039/d0np00045k

Cited by 26 publications

(38 citation statements)

References 175 publications

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“…Intriguingly, a larger gene cluster spanning 90 kb of the ACTtoxin producing tangerine pathotype A. alternata Z7 genome was proposed to encode the ACT-gene cluster (Wang et al, 2016; Figure 4). Of particular note in this cluster is the presence of a HMG-CoA synthase and an enoyl-CoA hydratase, that are suggestive of a potential mechanism for installing an α,β-unsaturated isovalerate via a β-branching type mechanism (Walker et al, 2020). Results from isotope labeling experiments with 13 C labeled acetate are consistent with this hypothesis (Nakatsuka et al, 1990).…”

Section: Acr-toxinsupporting

confidence: 55%

Accessory Chromosome-Acquired Secondary Metabolism in Plant Pathogenic Fungi: The Evolution of Biotrophs Into Host-Specific Pathogens

et al. 2021

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Accessory chromosomes are strain- or pathotype-specific chromosomes that exist in addition to the core chromosomes of a species and are generally not considered essential to the survival of the organism. Among pathogenic fungal species, accessory chromosomes harbor pathogenicity or virulence factor genes, several of which are known to encode for secondary metabolites that are involved in plant tissue invasion. Accessory chromosomes are of particular interest due to their capacity for horizontal transfer between strains and their dynamic “crosstalk” with core chromosomes. This review focuses exclusively on secondary metabolism (including mycotoxin biosynthesis) associated with accessory chromosomes in filamentous fungi and the role accessory chromosomes play in the evolution of secondary metabolite gene clusters. Untargeted metabolomics profiling in conjunction with genome sequencing provides an effective means of linking secondary metabolite products with their respective biosynthetic gene clusters that reside on accessory chromosomes. While the majority of literature describing accessory chromosome-associated toxin biosynthesis comes from studies ofAlternariapathotypes, the recent discovery of accessory chromosome-associated biosynthetic genes inFusariumspecies offer fresh insights into the evolution of biosynthetic enzymes such as non-ribosomal peptide synthetases (NRPSs), polyketide synthases (PKSs) and regulatory mechanisms governing their expression.

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Section: Acr-toxinsupporting

confidence: 55%

Accessory Chromosome-Acquired Secondary Metabolism in Plant Pathogenic Fungi: The Evolution of Biotrophs Into Host-Specific Pathogens

et al. 2021

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“…There are still PK/NRP biosynthesis pathways where the mechanism of chain release is unclear (for instance in squalistatin S1, bongkrekic acid and isoquinoline alkaloid biosynthesis). [271][272][273] In regards to TE domains, the evidence suggests that they are intrinsically able to catalyse a range of different release mechanisms, including hydrolysis, macrocyclization, oligomerisation, and transesterication. 23 Given this, how TE domains ultimately specialise to release only a single product is known.…”

Section: Final Remarksmentioning

confidence: 99%

Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis

Little

Hertweck

2022

Nat. Prod. Rep.

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“…The accessory proteins LasCDRS include enzymes known to be involved in ߚ-branch formation at module 1 and 10 ( 21). The ACPs at module 1 and 10 contain a conserved tryptophan which is involved in interacting with β-branching enzymes (37,38). LasR was identified to be responsible for dehydration (ECH1) while LasH ECHb and LasO ECHb to be responsible for decarboxylation (ECH2) during β-formation (39) (Fig.…”

Section: S3amentioning

confidence: 99%

Uncovering Lasonolide A biosynthesis using genome-resolved metagenomics

Uppal

Metz

Xavier

et al. 2022

Preprint

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Invertebrates, in particular sponges, have been a dominant source of new marine natural products. For example, lasonolide A (LSA) is a potential anti-cancer molecule isolated from the marine sponge Forcepia sp., with nanomolar growth inhibitory activity and a unique cytotoxicity profile against the National Cancer Institute 60 cell line screen. Here, we identified the putative biosynthetic pathway for LSA. Genomic binning of the Forcepia sponge metagenome revealed a gram-negative bacterium belonging to the phylum Verrucomicrobia as the candidate producer of LSA. Phylogenetic analysis showed this bacterium, herein named Candidatus Thermopylae lasonolidus, only has 88.78% 16S rRNA identity with the closest relative Pedosphaera parvula Ellin514, indicating it represents a new genus. The lasonolide A (las) biosynthetic gene cluster (BGC) was identified as a trans-AT polyketide synthase (PKS) pathway. When compared with its host genome, the las BGC exhibits a significantly different GC content and penta-nucleotide frequency, suggesting a potential horizontal acquisition of the gene cluster. Furthermore, three copies of the putative las pathway were identified in the candidate producer genome. Differences between the three las repeats were observed including the presence of three insertions, two single-nucleotide polymorphisms and the absence of a stand-alone acyl carrier protein in one of the repeats. Even though the Verrucomicrobial producer shows signs of genome-reduction, its genome size is still fairly large (about 5Mbp) and when compared to its closest free-living relative contains most of the primary metabolic pathways, suggesting that it is in the early stages of reduction.

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Polyketide β-branching: diversity, mechanism and selectivity

Abstract: The structural diversity of newly discovered polyketides continues to grow. This review summarises the range of structures with single and multiple β-branches and the mechanistic details of each catalytic step, covering literature from 2008 to August 2020.

Cited by 26 publications

References 175 publications

Accessory Chromosome-Acquired Secondary Metabolism in Plant Pathogenic Fungi: The Evolution of Biotrophs Into Host-Specific Pathogens

Accessory Chromosome-Acquired Secondary Metabolism in Plant Pathogenic Fungi: The Evolution of Biotrophs Into Host-Specific Pathogens

Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis

Uncovering Lasonolide A biosynthesis using genome-resolved metagenomics

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