ABSTRACT
Squalene is a widely distributed natural triterpene, as it is a key precursor in the biosynthesis of all sterols. It is a compound of high commercial value worldwide because it has nutritional, medicinal, pharmaceutical, and cosmetic applications, due to its different biological properties. The main source of extraction has been shark liver oil, which is currently unviable on a larger scale due to the impacts of overexploitation. Secondary sources are mainly vegetable oils, although a limited one, as they allow low productive yields. Due to the diversity of applications that squalene presents and its growing demand, there is an increasing interest in identifying sustainable sources of extraction. Wild species of thraustochytrids, which are heterotrophic protists, have been identified to have the highest squalene content compared to bacteria, yeasts, microalgae, and vegetable sources. Several studies have been carried out to identify the bioprocess conditions and regulation factors, such as the use of eustressors that promote an increase in the production of this triterpene; however, studies focused on optimizing their productive yields are still in its infancy. This review includes the current trends that also comprises the advances in genetic regulations in these microorganisms, with a view to identify the culture conditions that have been favorable in increasing the production of squalene, and the influences that both bioprocess conditions and applied regulation factors partake at a metabolic level.
Subject(s)
Squalene , Stramenopiles , Squalene/metabolism , Plant Oils , Stramenopiles/genetics , Stramenopiles/metabolism , SterolsABSTRACT
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.