Natural products (NPs) derived from diverse living organisms, including plants, animals, fungi, and bacteria, play an important role in presenting novel chemical structures and valuable biological activities. It is crucial to look for new modifying enzymes in order to increase the variety of NPs. We focus on car biosynthetic gene cluster (car BGC) because it encodes enzymes homologous to reported arginine-containing cyclodipeptide synthases (RCDPS) and α-KG dependent enzymes. Utilizing both in vitro assay and in vivo transformation, we found that car BGC is responsible for the biosynthesis of an arginine-derived compound, a relatively rare class from fungi; importantly, the enzymatic modifications on this arginine-derived compound are also elucidated. The structure of the compound is interesting because its backbone comprises the diketopiperazine (DKP) structures, and the ease of modification on the DKP holds promise for future research into new structural motifs and the exploration of diverse bioactivities.

The last decade has seen significant progress in identifying sleep mechanisms that support cognition. Most of these studies focus on the link between electrophysiological events of the central nervous system during sleep and improvements in different cognitive domains, while the dynamic shifts of the autonomic nervous system across sleep have been largely overlooked. Recent studies, however, have identified significant contributions of autonomic inputs during sleep to cognition. Yet, there remain considerable gaps in understanding how central and autonomic systems work together during sleep to facilitate cognitive improvement. My dissertation work investigates the independent and interactive roles of central and autonomic activities during sleep and wake in cognitive processing. I specifically focus on the prefrontal-subcortical working memory (WM) processing and mechanisms underlying the formation of hippocampal-dependent episodic long-term memory (LTM). Here, I first present an introduction to heart-brain interaction and memory processing during sleep. Next, I show two experimental studies where I examine the role of autonomic activities and autonomic-central couplings during sleep on WM, which has reliably been shown to benefit from sleep. Lastly, I present a pharmacological within-subjects, double-blind, placebo-controlled study that identifies separate and competing underlying mechanisms between autonomic and central activities supporting WM and LTM. In light of these three studies’ novel contributions, I propose a theoretical model – the Sleep Oscillation Switch (SOS) Model that sleep is a competitive arena in which autonomic WM and LTM vie for limited resources.