Reviews: JBC

Break down the algae. A piece of the centromere recruitment puzzle. Making pain relievers out of germs. Read articles on these and other topics recently published in the Journal of Biological Chemistry.

Degrading algae: an alternative enzymatic cascade

Marine algae are responsible for half of the world’s production of photosynthetic carbohydrates. The Ulva species – commonly known as sea lettuce – grows rapidly and produces large amounts of carbohydrate-rich biomass, making it an emerging renewable energy and carbon resource.

W. Carter / Wikimedia Commons

Gutweed is just one of many types of green algae. Marine animals, including manatees, and humans have incorporated sea lettuce into their diets.

To harness this potential energy source, researchers need to better understand the metabolic processes leading to the breakdown of algae by nature’s microbes. This is what motivated Marcus Bäumgen, Theresa Dutschei and their colleagues at the German University of Greifswald to undertake a recent study published in the Journal of Biological Chemistry.

A few years ago, the same team reported a complex enzyme cascade that allows a marine flavobacterium to degrade the ulvan algal polysaccharide. In the new JBC newspaper, Greifswald’s team reported their discovery of a distinct degradation pathway for ulvan oligosaccharides in the same marine bacteria, Formosa agariphila. The authors found a new dehydratase – P29_PDnc – acting on the non-reducing end of ulvan oligosaccharides.

“This elucidation of an alternative degradation pathway illustrates the complexity of biological systems for degradation of marine ulvans,” the authors wrote. “This indicates the need for back-up mechanisms for metabolic processes in order to access and compete for the diversity of complex sources of marine carbon in nature.”

The team’s research shows that this dehydratase is involved in the breakdown of carboxylated polysaccharides into monosaccharides, providing additional insight into the molecular mechanisms of the ocean’s carbon cycle.

“The characterizations of the enzymes active on ulvans and the clarification of their substrate extents allow these enzymes to be used for the production of ulvan-derived chemicals from currently rarely used green algal biomass,” wrote writers.

A piece of the centromere recruiting puzzle

Transcription of non-coding RNA at the centromere, a chromosomal locus essential for precise chromosome segregation during cell division, is an important step for proper centromere function. Alterations in this function lead to genomic instability and aneuploidy, commonly seen in human cancers.

Shuhei Ishikura and colleagues at Fukuoka University in Japan in 2020 determined that the zinc finger transcriptional regulator ZFAT binds to the centromere to regulate the transcription of ncRNAs. However, it has not been clear how ZFAT is recruited into the centromere.

Recently, the team reported in JBC that the centromeric protein CENP-B is an essential player in this process.

The authors performed ectopic expression and co-immunoprecipitation analysis, suggesting that ZFAT requires and interacts with CENP-B for ncRNA transcription. CENP-B knockdown showed decreased levels of ncRNA expression at the centromere.

“In addition, the obvious interaction between ZFAT and CENP-B has been observed in human and murine cells,” they wrote.

The researchers conclude that CENP-B helps establish the centromeric localization of ZFAT to regulate the transcription of ncRNAs.

Gender differences in glucose homeostasis

Metabolic syndrome is a group of conditions that increase the risk of heart disease, stroke, and diabetes. It is well established that sex as a physiological factor is strongly associated with metabolic syndrome.

Hv1 is a voltage-gated proton channel involved in insulin secretion. Huimin Pang and his colleagues at the University of Nankai in China have previously shown that male mice with knocked out Hv1 end up exhibiting hyperglycemia and insulin intolerance. But they wanted to know if this was also true for female knockout mice and, whether or not, what role sex steroids play in the results.

The team recently reported that in fact, fasting blood sugar levels in women were lower than in men despite decreased insulin secretion in both sexes. In addition, they found that knockout mice of both sexes exhibited increased expression of gluconeogenesis-related genes in the liver compared to wild-type mice.

This gender-related difference in glucose homeostasis is associated with glucose metabolism in liver tissue, the authors say, possibly due to physiological levels of testosterone in male knockout mice.

Making pain relievers out of germs

The pain relievers codeine and morphine are closely related benzylisoquinoline alkaloids, or BIAs, derived from the opium poppy. The microbial biosynthetic systems to produce these drugs are an area of ​​active research, as agricultural methods are affected by climate, supply chain and geopolitical instability. But this emerging synthetic biology strategy requires a detailed understanding of the biosynthetic pathway in the plant.

Codeinone reductase, or COR, catalyzes the last step in the biosynthetic pathway, but the determinants involved in substrate recognition and catalysis are not well defined.

Samuel C. Carr and his colleagues at the University of Calgary in Canada recently reported the crystal structure of apo-COR in the Journal of Biological Chemistry.

They made structural comparisons with closely related plant aldo-keto reductases, or AKRs, and distant homologs, revealing a new conformation in one of the loops adjacent to the BIA binding pocket. The authors used site-directed mutagenesis and identified specific substitutions in COR that led to changes in AKR activity for both substrates, codeinone and neopinone.

The authors wrote: “Further understanding of structure-function relationships in COR should lead to further improvements in the performance of microbial BIA biosynthesis systems. … Although still not commercially viable, microbial biosynthesis systems are rapidly gaining ground over traditional agricultural methods of obtaining these drugs and will one day lead to a pharmaceutical production process (which) is more environmentally friendly. environment, globally fair and easier to protect against illicit diversion. “


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