Method for Obtaining Microbial Secondary Metabolites or Derivatives Thereof by Heterologous Expression of at Least One Synthetase of Said Secondary Metabolites in Filamentous Fungi

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent describes a method for producing microbial secondary metabolites, particularly cyclodepsipeptides and their derivatives, by expressing specific synthetase enzymes from various sources in filamentous fungi such as Aspergillus, Trichoderma, Penicillium, Fusarium, or Rhizopus species. The procedure utilizes heterologous gene expression systems, including inducible and modular cassettes, to generate both native and novel hybrid (chimeric) secondary metabolites. The method also enables feeding of specific precursors to the culture or the engineering of the host to be independent of precursor supply. Additionally, it covers the construction of plasmid vectors, customized expression hosts, and the generation of isotopically labeled compounds for analytical uses.

Use CasesContent extracted from patent full text and abstract with AI.

• Industrial-scale production of valuable natural products such as antibiotics, antifungals, and immunosuppressive agents (e.g., enniatin, beauvericin).
• Creation of new-to-nature secondary metabolite analogs by engineering hybrid synthetases or feeding non-natural precursors.
• Production of isotopically labeled secondary metabolites for use as analytical standards in food safety and mycotoxin detection.
• Research tool in synthetic biology and metabolic engineering for pathway elucidation and combinatorial biosynthesis.
• Pharmaceutical development, including discovery and supply of novel compounds with improved or unique biological properties.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables efficient and scalable production of complex microbial natural products that are otherwise difficult to obtain from native producers.
• Facilitates the generation of novel analogs by modular domain swapping or precursor-directed biosynthesis.
• Allows for inducible, precise control of metabolite production via engineered expression cassettes.
• Improves yields over prior methods, making production more commercially viable.
• Flexible host range and the possibility to further engineer hosts for enhanced precursor supply, reducing the need for external feeding.
• Enables the creation of isotopically labeled standards critical for accurate quantitative analysis in the food and pharmaceutical industries.

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Patent Abstract

The present invention relates to a method for obtaining at least one microbial secondary metabolite or a derivative thereof, the method comprising the step of heterologous expression of at least one synthetase of said secondary metabolite in at least one filamentous fungus. Furthermore, the present invention relates to a expression cassette, a plasmid vector containing said expression cassette, an expression host, novel cyclodepsipeptides and a chimeric cyclodepsipeptide synthetase.