Identification and Functional Characterization of Fungal Chalcone Synthase and Chalcone Isomerase.

By mining fungal genomic information, a noncanonical iterative type I PKS fused with an N-terminal adenylation-thiolation didomain, which catalyzes the formation of naringenin chalcone, was found. Structural prediction and molecular docking analysis indicated that a C-terminal thioesterase domain was involved in the Claisen-type cyclization. An enzyme responsible for formation of (2)-flavanone in the biosynthesis of fungal flavonoids was also identified.

Discovery of a Cyclic Depsipeptide from by the Genome Mining Approach.

Genome mining and bioinformatics analyses allowed us to rationally find a candidate biosynthetic gene cluster for a new cyclic depsipeptide of . A heterologous reconstitution of the identified biosynthetic pathway predictably afforded a new cyclic depsipeptide composed of l-leucine, l-tryptophan, and a polyketide moiety. Interestingly, the 10-membered macrocycle structure generated equilibrium to an unprecedented cyclol structure.

Synthetic Biology-Based Discovery of Diterpenoid Pyrones from the Genome of .

Diterpenoid pyrones are a type of mainly fungal meroterpenoid metabolite consisting of a diterpene connected to a pyrone, some of which show potent bioactivity. Through genome mining and heterologous expression, nine new diterpenoid pyrones, shearones A-I (-), were discovered from the fungus IFM 42152, and their biosynthetic enzyme activities were revealed. Some of these heterologously biosynthesized diterpenoid pyrones exhibited moderate antiaggregative ability against amyloid β42 in vitro.

Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones.

A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera.

Post-genomic approach based discovery of alkylresorcinols from a cricket-associated fungus, Penicillium soppi.

Polyketide synthase (PKS) gene-guided genome mining in a cricket-associated fungus, Penicillium soppi, revealed a cryptic biosynthetic gene cluster that contained a highly reducing PKS (HR-PKS), a type III PKS, and a P450 gene. Heterologous expression of the cluster in Aspergillus oryzae led to the isolation of novel alkylresorcinols with a unique Z,E,Z-triene motif. This study displays an unusual biosynthetic mechanism of an HR-PKS and a new releasing mechanism via a type III PKS in fungi.

Use of a biosynthetic intermediate to explore the chemical diversity of pseudo-natural fungal polyketides.

The structural complexity and diversity of natural products make them attractive sources for potential drug discovery, with their characteristics being derived from the multi-step combination of enzymatic and non-enzymatic conversions of intermediates in each biosynthetic pathway. Intermediates that exhibit multipotent behaviour have great potential for use as starting points in diversity-oriented synthesis. Inspired by the biosynthetic pathways that form complex metabolites from simple intermediates, we developed a semi-synthetic process that combines heterologous biosynthesis and artificial diversification.