FAMIL­IAL ALS(Metagenomi)

Major advances have been made in the treatment of postmenopausal women with hormone-sensitive breast cancer. Although tamoxifen has been the standard endocrine therapy for the past twenty years, the development of a third generation of aromatase inhibitors (Als), which effectively inhibit estrogen synthesis in extragonadal sites, gives us a wider range of choices in endocrine therapy. However, many questions remain with respect to the optimal use of Als. Differences between Als and tamoxifen as well as non-steroidal and steroidal Als in their long-term adverse effects on bone demineralization and lipid metabolism are only starting to emerge. The preferable orders for use of non-steroidal and steroidal Als, Als and pure anti-estrogen in patients with metastatic disease are emerging subjects to be examined, following several studies that showed non-cross reactivity between these types of drug. Neo-adjuvant endocrine therapy is now attempting to apply breast conserving surgery in larger numbers of elderly patients who are not suitable for neo-adjuvant chemotherapy. Moreover, many investigators are currently searching for surrogate markers in neo-adjuvant endocrine treatment that can predict the responsiveness and prognosis with adjuvant endocrine therapy. Further research concomitant with clinical trials may lead to a more reliable endocrine therapy modality in the treatment of breast cancer.

Poly(lactate-co-3-hydroxybutyrate) [P(LA-co-3HB)] is a high-molecular-weight biomaterial with excellent biocompatibility and biodegradability. In this study, the properties of P(LA-co-3HB) were examined and found to be affected by its lactate fraction. The efficiency of lactyl-CoA biosynthesis from intracellular lactate significantly affected the microbial synthesis of P(LA-co-3HB). Two CoA transferases from Anaerotignum lactatifermentans and Bacillota bacterium were selected for use in copolymer biosynthesis from 11 candidates. We found that cotAl enhanced the lactate fraction by 31.56% compared to that of the frequently used modified form of propionyl-CoA transferase from Anaerotignum propionicum. In addition, utilizing xylose as a favorable carbon source and blocking the lactate degradation pathway further enhanced the lactate fraction to 30.42 mol% and 52.84 mol%, respectively. Furthermore, when a 5 L bioreactor was used for fermentation utilizing xylose as a carbon source, the engineered strain produced 60.60 wt% P(46.40 mol% LA-co-3HB), which was similar to the results of our flask experiments. Our results indicate that the application of new CoA transferases has great potential for the biosynthesis of other lactate-based copolymers.Graphical Abstract