Gene editing enables rapid engineering of complex antibiotic assembly lines.

Re-engineering biosynthetic assembly lines, including nonribosomal peptide synthetases (NRPS) and related megasynthase enzymes, is a powerful route to new antibiotics and other bioactive natural products that are too complex for chemical synthesis. However, engineering megasynthases is very challenging using current methods. Here, we describe how CRISPR-Cas9 gene editing can be exploited to rapidly engineer one of the most complex megasynthase assembly lines in nature, the 2.

Reconstitution of a Highly Reducing Type II PKS System Reveals 6π-Electrocyclization Is Required for -Dialkylbenzene Biosynthesis.

Natural products containing an -dialkylbenzene moiety exhibit a wide variety of bioactivities, including antibacterial, antifungal, antitumor, and antiangiogenic activities. However, the biosynthetic scheme of the -dialkylbenzene moiety remains unclear. In this study, we identified the biosynthetic gene cluster (BGC) of compounds and in sp.

First pediatric organ donation after circulatory determination of death in Singapore: Facing challenges in the absence of a local practice guideline.

Pediatric organ donation represents only a low proportion of overall organ donation in many parts of world, unable to match the needs for pediatric organ transplantation. Pediatric organ donation after circulatory determination of death (DCD) is increasingly explored in pediatric transplantation, as it increases the availability of organ grafts. A 6-year-old Caucasian boy with a history of arteriovenous malformation presented with a catastrophic intracranial bleed, resulting in severe brainstem dysfunction despite maximal medical and surgical measures.