Researchers from the Centro de Investigaciones Biológicas Margarita Salas in Madrid, led by Gabriel Hernández-Fernández, have made significant strides in the production of a valuable steroid compound, 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC), using the bacterium Mycolicibacterium smegmatis. This compound is considered a critical synthon for pharmaceuticals and is produced as a byproduct of natural sterol catabolism, which includes common substances like cholesterol and phytosterols.
In their study published in the journal Microbial Biotechnology, the team focused on the role of specific enzymes coded by the MSMEG_6563 and MSMEG_1623 genes in the conversion process of intermediate metabolites into 4-HBC. They found that the enzyme msRed, associated with the MSMEG_6563 gene, effectively reduces 3-oxo-4-pregnene-20-carboxyl aldehyde (3-OPA) to produce 4-HBC. While another enzyme, msOpccR, also contributes to this conversion, it does so at a lower efficiency.
To enhance the production capabilities of Mycolicibacterium smegmatis, the researchers engineered a mutant strain by deleting a specific gene (MSMEG_5903), which allowed the bacteria to produce 4-HBC more effectively. In their experiments, the modified strain produced an impressive 9 grams per liter of 4-HBC from 14 grams per liter of phytosterols in a 2-liter bioreactor, demonstrating a productivity rate of 0.140 grams per liter per hour. Further improvements were achieved by cloning and overexpressing the msSal and msRed enzymes, leading to a higher production yield of 12.7 grams per liter and a productivity of 0.185 grams per liter per hour.
Hernández-Fernández emphasized the potential commercial applications of this research, stating, “The new recombinant strain has a great potential for its industrial application.” This advancement could pave the way for more sustainable and efficient production methods for pharmaceutical compounds derived from natural sterols, which are increasingly in demand.
The implications of this research extend to various sectors, including pharmaceuticals, biotechnology, and sustainable manufacturing. By utilizing microbial processes to produce valuable compounds, companies can reduce reliance on traditional chemical synthesis methods, which often involve harsh conditions and toxic byproducts. As the pharmaceutical industry continues to seek greener alternatives, the findings from this study could play a crucial role in shaping future production strategies.
Overall, the work of Hernández-Fernández and his team marks a notable advancement in microbial biotechnology, offering promising avenues for the sustainable production of important steroid compounds.
