MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Heterologous Expression of Fungal Biosynthetic Pathways in Aspergillus nidulans Using Episomal Vectors.

Filamentous fungi produce a wide diversity of secondary metabolites, whose biosynthesis is encoded in biosynthetic gene clusters (BGCs). As novel BGCs are often found in fungal species that are genetically intractable or difficult to cultivate, heterologous expression is increasingly being used for compound discovery. In addition, heterologous expression is a useful strategy to elucidate the function of the genes within a BGC and shed light on their enzymatic mechanisms.

A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation.

Xantholipin and several related polycyclic xanthone antibiotics feature a unique xanthone ring nucleus within a highly oxygenated, angular, fused hexacyclic system. In this study, we demonstrated that a flavin-dependent monooxygenase (FMO) XanO4 catalyzes the oxidative transformation of an anthraquinone to a xanthone system during the biosynthesis of xantholipin. In vitro isotopic labeling experiments showed that the reaction involves sequential insertion of two oxygen atoms, accompanied by an unexpected cryptic demethoxylation reaction.

Functional redundancy of necrotrophic effectors - consequences for exploitation for breeding.

Necrotrophic diseases of wheat cause major losses in most wheat growing areas of world. Tan spot (caused by Pyrenophora tritici-repentis) and septoria nodorum blotch (SNB; Parastagonospora nodorum) have been shown to reduce yields by 10-20% across entire agri-ecological zones despite the application of fungicides and a heavy focus over the last 30 years on resistance breeding. Efforts by breeders to improve the resistance of cultivars has been compromised by the universal finding that resistance was quantitative and governed by multiple quantitative trait loci (QTL).

Discovery of cryptic polyketide metabolites from dermatophytes using heterologous expression in Aspergillus nidulans.

Dermatophytes belonging to the Trichophyton and Arthroderma genera cause skin infections in humans and animals. From genome sequencing data, we mined a conserved gene cluster among dermatophytes that are homologous to one that produces an immunosuppressive polyketide in Aspergillus fumigatus. Using a recombination-based cloning strategy in yeast, we constructed fungal heterologous expression vectors that encode the cryptic clusters.

Characterization of the Suillus grevillei quinone synthetase GreA supports a nonribosomal code for aromatic α-keto acids.

The gene greA was cloned from the genome of the basidiomycete Suillus grevillei. It encodes a monomodular natural product biosynthesis protein composed of three domains for adenylation, thiolation, and thioesterase and, hence, is reminiscent of a nonribosomal peptide synthetase (NRPS). GreA was biochemically characterized in vitro.