Ahmad Abdel-Mawgoud Saleh, Département de biochimie, de microbiologie et de bio-informatique
Chemical synthetic biology is a subdomain of synthetic biology that aims at transforming biological systems into platforms for the biosynthesis of a variety of target chemicals. The most important application of chemical synthetic biology is in drug production and drug discovery. There is a continuous need for human medicinal drugs, however, they originate from secondary metabolites of bacteria, fungi and mostly plants and are usually present in small quantities, hence, are costly to make available. One of the important targets of chemical synthetic biology is to engineer easy-to-grow industrial microbial hosts to produce these secondary metabolites in a more convenient way.
My group is interested in producing lipid-based biomolecules using chemical synthetic biology approaches in microbial hosts like lipogenic bacteria (e.g. Rhodococcus erythrolpolis) and yeasts (e.g. Yarrowia lipolytica). The lipid-based biomolecules we are interested in are small molecules having applications in biomedical, bioremediation and biofuel domains. Given that the biomolecules we are interested in are lipid-based, we use lipogenic microbial hosts as biological chassis for our synthetic biology procedures because of their natural high flux of lipid precursors, which we harness to biosynthesize added value derivatives destined for the above-mentioned applications. Currently, our focus is on producing biomolecules belonging to the simple glycolipids family whose members have interesting bioactivities, like antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities (A.M. Abdel-Mawgoud and G. Stephanopoulos, 2018).
In the short term, we are working on developing synthetic biology approaches for rhamnolipids production as lead glycolipid molecules that have interesting bioactivities and will also inspire the development of synthetic biology approaches for the production of other bioactive members of the glycolipids family.
For our long-term goals for glycolipids, they include: 1) To discover new natural glycolipids species using genome/metagenome mining for new glycosyl transferases expected to produce new species of glycolipids with variations in their lipid or glycosyl moieties and hence new bioactivities. 2) To biosynthesize new-to-nature glycolipids by engineering their biosynthetic enzymes, particularly glycosyl/acyl transferases, and by the assembly of chimeric biosynthetic pathways resulting in new glycolipids with potentially new bioactivities.
In the meantime, we work on advancing fundamental knowledge 1) to better understand the biosynthesis of glycolipids, 2) to characterize the key metabolic enzymes of the glycolipids biosynthetic pathways, particularly glycosyl and acyl transferases, 3) to better understand the biochemical mechanisms of lipid accumulations (lipogenesis) in lipogenic organisms. This improved understanding paves the way for the design of successful metabolic engineering strategies for efficient glycolipids production in microbial hosts.
Moreover, we work on extending the molecular biology toolkits available for different biological hosts (chassis) we are using. We are developing CRISPR/Cas9-based genome editing protocols in lipogenic yeasts. Moreover, we are optimizing gene expression machineries for the highest expression of metabolic enzymes participating in the biosynthesis of target biomolecules.
In addition to our interest in lipid-based biomolecules that improve human health, we also envision developing ecofriendly lipid-based molecules for bioremediation and biofuel industries. Lipogenic yeasts have abundant of fatty acids which when linked to polar groups, like sugars or short peptides, result in formation of amphiphilic molecules, like rhamnolipids and surfactins, with detergent properties that are useful for solubilizing oil contaminants in soil and marine environments. On another hand, we are also interested in converting the lipogenic yeast’s high fatty acid pool to fatty acid alkyl ester derivatives that act as biofuel and offer a sustainable/ecological solution to the non-renewable fossil fuels. To support an economically viable bioproduction process, a part of our work is to develop synthetic biology strategies that enable microbial hosts feed on cheap carbon sources, particularly lignocellulosic wastes.
For further information about our research activities, please consult the lab website: abdel-mawgoud.com