Novel approach could be faster, and cheaper, than making the cells in the lab—but safety concerns linger

Upon sensing nonself target RNA, the CorA-associated type III-B CRISPR–Cas system catalyzes S-adenosyl methionine (SAM) and ATP to synthesize SAM-AMP, which activates the effector CorA and triggers immune responses. SAM-AMP can be degraded by NrN and SAM lyase, potentially deactivating the system. Here we find that the type III-B effector complex from Bacteroides fragilis uses a specific mechanism to recognize nonself target RNA and synthesize SAM-AMP. The 3′ anti-tag of nonself target RNA induces conformational changes in the Cmr2 subunit, triggering SAM-AMP synthesis independently of the stalk loop of Cmr3 subunit. SAM-AMP binding induces NrN to transit from an open to a closed conformation, enabling hydrolysis of the 3′–5′ phosphodiester bond. SAM lyase forms a triangular trimer that specifically degrades SAM-AMP into 5′-methylthioadenosine-AMP and homoserine lactone. These findings unveil unique mechanisms for SAM-AMP synthesis and degradation and provide deeper insights into the m

An Open-Source web application for DNA engineering

Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1−/− mice are not obese1–5, consistent with the existence of alternative mechanisms of thermogenesis6–8. Here we describe a UCP1-independent mechanism of thermogenesis involving ATP-consuming metabolism of monomethyl branched-chain fatty acids (mmBCFA) in peroxisomes. These fatty acids are synthesized by fatty acid synthase using precursors derived from catabolism of branched-chain amino acids9 and our results indicate that β-oxidation of mmBCFAs is mediated by the peroxisomal protein acyl-CoA oxidase 2 (ACOX2). Notably, cold exposure upregulated proteins involved in both biosynthesis and β-oxidation of mmBCFA in thermogenic fat. Acute thermogenic stimuli promoted translocation of fatty acid synthase to peroxisomes. Brown-adipose-tissue-specific fatty acid synthase knockout decreased cold