Carbon catabolite regulation of secondary metabolite formation, an old but not well‐established regulatory system

Abstract

Summary Secondary microbial metabolites have various functions for the producer microorganisms, which allow them to interact and survive in adverse environments. In addition to these functions, other biological activities may have clinical relevance, as diverse as antimicrobial, anticancer and hypocholesterolaemic effects. These metabolites are usually formed during the idiophase of growth and have a wide diversity in their chemical structures. Their synthesis is under the impact of the type and concentration of the culture media nutrients. Some of the molecular mechanisms that affect the synthesis of secondary metabolites in bacteria (Gram‐positive and negative) and fungi are partially known. Moreover, all microorganisms have their peculiarities in the control mechanisms of carbon sources, even those belonging to the same genus. This regulatory knowledge is necessary to establish culture conditions and manipulation methods for genetic improvement and product fermentation. As the carbon source is one of the essential nutritional factors for antibiotic production, its study has been imperative both at the industrial and research levels. This review aims to draw the utmost recent advances performed to clarify the molecular mechanisms of the negative effect exerted by the carbon source on the secondary metabolite formation, emphasizing those found in Streptomyces, one of the genera most profitable antibiotic producers.

Oropharynx microbiota transitions in hypopharyngeal carcinoma treatment of induced chemotherapy followed by surgery

“…The versatile composition of human microbiota could enrich and stabilize the micro-environment. Personal habits or different biomedical processes such as metabolism [6], immune status [7], energy intake, and cell status [8] may heavily influence microbial composition. As a significant source of the genome, microbial communities could be used as a metric to assess the overall physical conditions of patients.…”

Dissecting the role of the two Streptomyces peucetius var. caesius glucokinases in the sensitivity to carbon catabolite repression

“…Looking at the ATP-Glk amino acid sequence, a lack of DNA-binding motifs in this enzyme is detected. Therefore, as recently suggested (Ruiz-Villafán et al, 2021 ), its action mechanism likely requires additional proteins or cofactors to be performed. In S. coelicolor , even though the ATP-Glk also lacks DNA-binding motifs, the enzyme specifically affects the expression of 43 genes by a mechanism that awaits to be defined (Romero-Rodríguez et al, 2016 ).…”

Effects of dual deletion ofglnRandmtrAon expression of nitrogen metabolism genes inStreptomyces venezuelae

“…Streptomyces can produce a vast variety of secondary metabolites of clinical importance, including antibiotics, antifungals, antihelminthics, antivirals and immunosuppressives (Hopwood, 2007). Production of secondary metabolites is controlled by cascades of regulatory factors at different levels in response to environmental changes such as nutrient shifts, including shifts in carbon and nitrogen levels (Hoskisson & Fernandez‐Martinez, 2018, Ruiz‐Villafan et al ., 2021). Primary metabolism, such as central carbon metabolism, not only supports cell growth but also provides precursors for secondary metabolism; for example, carbon catabolism regulates formation of secondary metabolites including antibiotics (Ruiz‐Villafan et al ., 2021).…”

“…Production of secondary metabolites is controlled by cascades of regulatory factors at different levels in response to environmental changes such as nutrient shifts, including shifts in carbon and nitrogen levels (Hoskisson & Fernandez‐Martinez, 2018, Ruiz‐Villafan et al ., 2021). Primary metabolism, such as central carbon metabolism, not only supports cell growth but also provides precursors for secondary metabolism; for example, carbon catabolism regulates formation of secondary metabolites including antibiotics (Ruiz‐Villafan et al ., 2021). Similarly, nitrogen is not only required for robust cellular growth but also as a component for nitrogen‐containing secondary metabolites, and therefore, the availability and sources of nitrogen govern the production of secondary metabolites (Voelker & Altaba, 2001).…”