Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly expanding family of natural products in which biosynthetic maturase enzymes tailor ribosomal precursors into bioactive products. Classical RiPP maturation relies on an N-terminal leader sequence in the precursor peptide and a complementary RiPP-recognition element in the enzyme to guide substrate binding. Herein, we interrogated PapB, a radical S-adenosyl-l-methionine RiPP maturase known to introduce thio(seleno)-ether cross-links and discovered that its catalytic reach extends well beyond this paradigm. PapB efficiently processes substrates that lack any canonical leader sequence, demonstrating bona fide leader-independent activity. To highlight the practical value of this capability, we applied PapB to three therapeutically relevant analogues of glucagon-like peptide pathway agonists to generate C-terminal cyclic structures. In every case, the enzyme achieved complete conversion of the linear to the thioether macrocyclized peptide. These results establish PapB as a versatile, plug-and-play biocatalyst for late-stage macrocyclization of structurally diverse peptides, opening a direct route to conformationally constrained therapeutic candidates without the need for leader tags.

Researchers at Huntsman Cancer Institute found that lipids fuel growth in triple-negative breast cancer cells. High-fat diets like keto could unintentionally worsen outcomes for breast cancer patients...

Background and ObjectivesIntrathecal synthesis of immunoglobulin G (IgG) is a key feature of multiple sclerosis (MS) and a prognostic marker for the disease course. Although previous studies identifie...

This paper reports the expert opinions and recommendations made by primary care physicians (PCPs) to optimize screening and management of chronic kidney di

Treatment decisions for type 2 diabetes are complex and multifactorial. This study evaluated the utility of OpenAI’s generative pre-trained transformer-4 (

Materials scientists can learn a lot about a sample material by shooting lasers at it. Nonlinear optical microscopy — a specialized imaging technique that looks for a change in the color of intense la...

Net winged beetles (Lycidae) are cosmopolitan pollinators, known for their intricate vein-like wing patterns and eye-catching colours, but behind these diverse delicate beetles lies an evolutionary en...

A nanophotonic cavity based on topological synthetic dimension design demonstrates high-performance rainbow lasing.

The metabots resemble animated sheets of plastic, capable of moving around a surface or grasping objects.

Closely matching its human counterpart, replica eliminates need for animal testing

This comparative effectiveness study examines major adverse cardiovascular events among patients with type 2 diabetes receiving sulfonylureas, dipeptidyl peptidase-4 (DPP4) inhibitors, sodium-glucose ...

Analyses of newly discovered hand and foot bones of a Paranthropus boisei specimen provide insight into possible tool use and other palaeobiology characteristics among Plio-Pleistocene hominin species...

AbstractBackground and Aims. Atrial cardiomyopathy (AtCM) is increasingly recognized as an important substrate for atrial fibrillation (AF). This study aim

Transformer models are adaptable to off-the-beaten-path molecular design tasks, such as protein-sequence-based compound design. The authors use these predictions as a model system to unravel the learn...

A perspective published in Science argues that scientific evidence clearly supports the coca leaf as a benign, useful, and culturally paramount crop plant that should be removed from the list of Sched...

How old is our water?

Despite advances in targeted therapies, treatment with glucocorticoids remains a mainstay in the management of various immune-mediated diseases. High cumulative doses of exogenous glucocorticoids lead...

Pulsars suggest that ultra–low-frequency gravitational waves are rippling through the cosmos. The signal seen by international pulsar timing array collaborations in 2023 could come from a stochastic gravitational-wave background—the sum of many distant sources—or from a single nearby binary of supermassive black holes.

The widespread distribution of the Sauveterrian complex across Europe suggests the presence of networks connecting distant groups, facilitating the di…

With rising global attention to health and the accelerating trend of population aging, the demand for Foods for Special Medical Purposes (FSMPs) has i…

Carotid atherosclerosis is a significant cause of incident and recurrent ischemic stroke, with risk not solely related to the degree of luminal stenosis. Multimodal imaging approaches, including posit...