In order to replace some petrochemical derivatives with less polluting molecules, strategies were developed for the production of new oleochemical compounds. At present, most of the oleochemicals produced are of plant origin, however, in recent years microorganisms have begun to be used as “biorefineries” for the production of lipid molecules for industrial use ranging from esters, alcohols , alkanes to fatty acids (FA) with special properties. In reference to the compounds derived from AG, it is important to highlight that the physicochemical properties, and therefore the use of these compounds, is largely defined by the structural characteristics of the AG that form it. In this sense, the unsaturated FA, although they improve the fluidity of the compounds, they are easily oxidizable. On the other hand, saturated FA, although they are resistant to oxidation, have low yields and performance at low temperatures. In order to obtain FA, and derivatives thereof, with greater steric hindrance to improve their fluidity at low temperatures, but maintaining their stability, our proposal is to produce methyl-branched FA in bacteria. To do this, we will develop a platform based on E. coli capable of synthesizing these compounds by altering their natural FA synthesis process, expressing new metabolic pathways obtained from different Actinomycetes. Directors: Ana Arabolaza and Hugo Gramajo.

Biochemical and genetic studies of fatty acid activation mechanisms in Actinomycetes

The central proposal of this line is to elucidate the relevance of fatty acid (FA) activation mechanisms in actinomycetes. The most widespread FA activation reaction involves their conversion to the corresponding coenzyme A derivatives (CoASH), which is catalyzed by a family of ubiquitous enzymes: FACL (fatty acyl-CoA ligase). However, in actinomycetes and various pathogenic microorganisms such as Chlamydia trachomatis and Neisseria gonorrhoeae, there is an alternative mechanism where FA can be converted into acyl-ACP. The enzymes in charge of this step are FAAS (fatty acyl-ACP synthetases) that convert FA into acyladenylates which then acylate the acyl carrier: ACP proteins or ACP domains in polyketide synthases (PKS) to biosynthesize, for example, secondary metabolites or complex lipids. Thus, FAAS represent an important point of coordination between primary and secondary metabolism in actinomycetes. In addition, some members of this large family, particularly FAAL (Fatty Acyl-AMP Ligases) have been validated as targets for the development of new antimycobacterials. Currently it is not possible to discriminate between FAAS and FACL enzymes by studies based on their protein sequences, being necessary a biochemical validation to distinguish them. This is why we propose to carry out genetic and biochemical studies to characterize the physiological role of some selected candidates of this type of enzymes.

Production of natural products by Actinobacteria

The bacteria of the Actinomycetes group have provided more than two thirds of the natural products for therapeutic use, with 80% of these compounds being produced by bacteria of the Streptomyces genus. In this line of research, we are focused on the search for new compounds with biological properties of therapeutic interest. We are carrying out different “Bioguided strategies for the identification of new antimicrobial agents”. On the one hand, we are analyzing the identification of antifungal compounds produced by rhizosphere bacteria for use in seed treatments. On the other hand, and in collaboration with Dr. Eleonora García Vescovi and Dr. Leticia Llarull, we are searching for natural compounds from Streptomyces strains that will have modulatory activity on different two-component systems of Salmonella typhimurium and Staphylococcus aureus involved in the virulence or pathogenicity of said bacteria. Dr. Eduardo Rodríguez.

Development of Actinobacteria as biocontrol agents

In this line of research, we address the problem in the decline that originates in agricultural production, as is the case of soybean cultivation, due to biotic stress caused by different phytopathogenic fungi. Currently, to control these diseases, chemical fungicides are applied prior to sowing. However, its use is increasingly restricted and discussed, due to the toxic and harmful effects on human health and the environment. As an alternative, new treatment with microorganisms that induce a protective effect on crops or biocontrol have emerged. In this project we seek the development of biocontrol agents based on Streptomyces strains isolated from the rhizosphere of soybean plants. These strains were characterized by their properties to inhibit phytopathogenic fungi as well as promoters of crop growth. Currently we are not deepening the knowledge of biological control mechanisms and the promotion of growth by these strains, as studying the importance of the production of antifungal compounds in biocontrol. On the other hand, it seeks to optimize their production and formulation with the intention of replacing traditional seed cures and thus reduce the environmental impact of their use. We carried out these studies with the collaboration of Dr. M. Amalia Chie