AI Article Synopsis
- Some mycobacteria species can be genetically modified to convert sterols into useful steroid synthons, aided by their unique cell wall that effectively absorbs sterols.
- Using cell wall inhibitors like vancomycin and glycine has shown to boost sterol conversion by disrupting a key step in their cell wall synthesis.
- Altering specific genes (pbpA and pbpB) in the mycobacteria resulted in significant changes in cell morphology and a 28% increase in the production of a steroid compound (4-HBC), demonstrating that modifying the cell wall can enhance sterol utilization.
Article Abstract
Some species of mycobacteria have been modified to transform sterols to valuable steroid synthons. The unique cell wall of mycobacteria has been recognized as an important organelle to absorb sterols. Some cell wall inhibitors (e.g., vancomycin and glycine) have been validated to enhance sterol conversion by interfering with transpeptidation in peptidoglycan biosynthesis. Therefore, two transpeptidase genes, pbpA and pbpB, were selected to rationally modify the cell wall to simulate the enhancement effect of vancomycin and glycine on sterol conversion in a 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) producing strain (WIII). Unexpectedly, the pbpA or pbpB gene augmentation was conducive to the utilization of sterols. The pbpB augmentation strain WIII-pbpB was further investigated for its better performance. Compared to WIII, the morphology of WIII-pbpB was markedly changed from oval to spindle, indicating alterations of the cell wall. Biochemical analysis indicated that the altered cell wall properties of WIII-pbpB might contribute to the positive effect on sterol utilization. The productivity of 4-HBC was enhanced by 28% in the WIII-pbpB strain compared to that of WIII. These results demonstrated that the modification of peptidoglycan synthesis can improve the conversion of sterols to steroid synthons in mycobacteria.
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| http://dx.doi.org/10.1002/jobm.201900159 | DOI Listing |
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