Progress in endophytic fungi secondary metabolites: biosynthetic gene cluster reactivation and advances in metabolomics

Bulletin of the National Research Centre

Table 2 Strategies used to activate silent BGCs

Strategy	Advantages	Disadvantages	References
Environmental stimuli	Simple, does not require molecular methods, and can be used on unexplored species	It is not specific, alters many clusters, requires genetic modifications	Reen et al. (2015)
Global regulator	An easy method of activating several cluster activation pathways to increase the amount of metabolites	It is not specific, affects many clusters, and requires genetic modifications	Shim (2020); Pillay et al. (2022)
Cluster-specific transcription factor	Targets a specific BGC, requires only one gene to be manipulated	Requires genetic modifications and requires a cluster with a transcription factor	Kjærbølling et al. (2019)
Promoter engineering	It can activate a single BGC gene expression, can be used on full clusters, and does not require a transcription factor	Laborious, time-consuming and requires genetic modifications	Liu et al. (2021a, b)