Maleidrides are a family of structurally related fungal natural products, many of which possess diverse, potent bioactivities. Previous identification of several maleidride biosynthetic gene clusters, and subsequent experimental work, has determined the 'core' set of genes required to construct the characteristic medium-sized alicyclic ring with maleic anhydride moieties. Through genome mining, this work has used these core genes to discover ten entirely novel putative maleidride biosynthetic gene clusters, amongst both publicly available genomes, and encoded within the genome of the previously un-sequenced epiheveadride producer Wicklowia aquatica CBS 125634. We have undertaken phylogenetic analyses and comparative bioinformatics on all known and putative maleidride biosynthetic gene clusters to gain further insights regarding these unique biosynthetic pathways.
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http://dx.doi.org/10.1186/s40694-022-00132-z | DOI Listing |
Nat Prod Rep
January 2023
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
Covering: up to early 2022Maleidrides are a family of polyketide-based dimeric natural products isolated from fungi. Many maleidrides possess significant bioactivities, making them attractive pharmaceutical or agrochemical lead compounds. Their unusual biosynthetic pathways have fascinated scientists for decades, with recent advances in our bioinformatic and enzymatic understanding providing further insights into their construction.
View Article and Find Full Text PDFassays of enzymes involved in the biosynthesis of maleidrides from polyketides in fungi were performed. The results show that the enzymes are closely related to primary metabolism enzymes of the citric acid cycle in terms of stereochemical preferences, but with an expanded substrate selectivity. A key citrate synthase can react both saturated and unsaturated acyl CoA substrates to give solely substituted citrates.
View Article and Find Full Text PDFFungal Biol Biotechnol
February 2022
School of Biological Sciences, Life Sciences Building, University of Bristol, 24 Tyndall Ave, Bristol, BS8 1TQ, UK.
Maleidrides are a family of structurally related fungal natural products, many of which possess diverse, potent bioactivities. Previous identification of several maleidride biosynthetic gene clusters, and subsequent experimental work, has determined the 'core' set of genes required to construct the characteristic medium-sized alicyclic ring with maleic anhydride moieties. Through genome mining, this work has used these core genes to discover ten entirely novel putative maleidride biosynthetic gene clusters, amongst both publicly available genomes, and encoded within the genome of the previously un-sequenced epiheveadride producer Wicklowia aquatica CBS 125634.
View Article and Find Full Text PDFJ Fungi (Basel)
August 2018
Leibniz Universität Hannover, Biomolekulares Wirkstoffzentrum und Institut für Organische Chemie, Schneiderberg 38, 30167 Hannover, Germany.
is traditionally used in East Asia for the production of food and brewing. In addition, it has been developed into a suitable host for the heterologous expression of natural product biosynthetic genes and gene clusters, enabling the functional analysis of the encoded enzymes. shares a 99.
View Article and Find Full Text PDFChem Commun (Camb)
July 2017
Institute for Organic Chemistry, and BMWZ, Leibniz University of Hannover, Schneiderberg 1B, 30167, Germany.
The biosynthesis of the herbicide cornexistin in the fungus Paecilomyces variotii was investigated by full sequencing of its genome, knockout of key genes within its biosynthetic gene cluster and isolation and identification of intermediate compounds. The general biosynthetic pathway resembles that of byssochlamic acid and other nonadrides in the early stages, but differs in requiring fewer enzymes in the key nonadride dimerisation step, and in the removal of one maleic anhydride moiety.
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