FIGURE 1.

Synthetic biology strategies for natural product production in filamentous fungi. Different strategies that could be used to activate computationally identified gene clusters: (A) Manipulation of different elements of signal transduction pathways leading to novel or different regulation of NPs. The activation (by phosphorylation) of transcription factors (TF), global or NP gene cluster specific, can be achieved by specific stimuli (signal), engineering of protein kinases (PK), or deletion of signal repressors such as protein phosphatases (PP); (B) Heterologous expression of known or unknown NP gene clusters in an amenable host to achieve production of novel/bioactive NPs. This includes the assembly of a plasmid containing the necessary/putative genes involved and then transformation and heterologous expression to achieve production; (C) Domain swapping of different parts of multidomain biosynthetic enzymes such as PKSs. Different aspects such as the swapping of the C or N terminal domains have been accomplished for production of novel NPs.