Engineering of global transcription factors in Bacillus, a genetic tool for increasing product yields: a bioprocess overview

Transcriptional factors are well studied in bacteria for their global interactions and the effects they produce at the phenotypic level. Particularly, Bacillus subtilis has been widely employed as a model Gram-positive microorganism used to characterize these network interactions. Bacillus species are currently used as efficient commercial microbial platforms to produce diverse metabolites such as extracellular enzymes, antibiotics, surfactants, industrial chemicals, heterologous proteins, among others. However, the pleiotropic effects caused by the genetic modification of specific genes that codify for global regulators (transcription factors) have not been implicated commonly from a bioprocess point of view. Recently, these strategies have attracted the attention in Bacillus species because they can have an application to increase production efficiency of certain commercial interest metabolites. In this review, we update the recent advances that involve this trend in the use of genetic engineering (mutations, deletion, or overexpression) performed to global regulators such as Spo0A, CcpA, CodY and AbrB, which can provide an advantage for the development or improvement of bioprocesses that involve Bacillus species as production platforms. Genetic networks, regulation pathways and their relationship to the development of growth stages are also discussed to correlate the interactions that occur between these regulators, which are important to consider for application in the improvement of commercial-interest metabolites. Reported yields from these products currently produced mostly under laboratory conditions and, in a lesser extent at bioreactor level, are also discussed to give valuable perspectives about their potential use and developmental level directed to process optimization at large-scale. [GRAPHICS] .

Automated summary

Transcriptional factors in bacteria, especially Bacillus species, have been extensively studied for their global interactions and effects on phenotypic levels. These factors play a crucial role in the regulation of commercial-interest metabolites production in Bacillus species. Genetic engineering of global regulators such as Spo0A, CcpA, CodY, and AbrB has shown potential for improving bioprocesses involving Bacillus species as production platforms. However, the pleiotropic effects caused by genetic modification of these regulators have not been commonly considered in the bioprocess context. This review provides an update on recent advances in this field and discusses the importance of genetic networks, regulation pathways, and their relationship to growth stages in enhancing the production efficiency of commercial-interest metabolites.