Improved pestalotiollide B production by deleting competing polyketide synthase genes in Pestalotiopsis microspora.

Pestalotiollide B, an analog of dibenzodioxocinones which are inhibitors of cholesterol ester transfer proteins, is produced by Pestalotiopsis microspora NK17. To increase the production of pestalotiollide B, we attempted to eliminate competing polyketide products by deleting the genes responsible for their biosynthesis. We successfully deleted 41 out of 48 putative polyketide synthases (PKSs) in the genome of NK17. Nine of the 41 PKS deleted strains had significant increased production of pestalotiollide B (P < 0.05). For instance, deletion of pks35, led to an increase of pestalotiollide B by 887%. We inferred that these nine PKSs possibly lead to branch pathways that compete for precursors with pestalotiollide B, or that convert the product. Deletion of some other PKS genes such as pks8 led to a significant decrease of pestalotiollide B, suggesting they are responsible for its biosynthesis. Our data demonstrated that improvement of pestalotiollide B production can be achieved by eliminating competing polyketides.

Aerospace Technology Improves Fermentation Potential of Microorganisms.

It is highly possible to obtain high-quality microbial products in appreciable amounts, as aerospace technology is advancing continuously. Genome-wide genetic variations in microorganisms can be triggered by space microgravity and radiation. Mutation rate is high, mutant range is wide, and final mutant character is stable. Therefore, space microorganism breeding is growing to be a new and promising area in microbial science and has greatly propelled the development of fermentation technology. Numerous studies have discovered the following improvements of fermentation potential in microorganisms after exposure to space: (1) reduction in fermentation cycle and increase in growth rate; (2) improvement of mixed fermentation species; (3) increase in bacterial conjugation efficiency and motility; (4) improvement of the bioactivity of various key enzymes and product quality; (5) enhancement of multiple adverse stress resistance; (6) improvement of fermentation metabolites, flavor, appearance, and stability. Aerospace fermentation technology predominantly contributes to bioprocessing in a microgravity environment. Unlike terrestrial fermentation, aerospace fermentation keeps cells suspended in the fluid medium without significant shear forces. Space radiation and microgravity have physical, chemical, and biological effects on mutant microorganisms by causing alternation in fluid dynamics and genome, transcriptome, proteome, and metabolome levels.