Protein malnutrition remains a major global health challenge, particularly in regions where cereal grains dominate daily diets and access to diverse protein sources is limited. Cereals such as rice, wheat and maize provide most of the world’s calories, yet their grain proteins are often low in essential amino acids and poorly balanced for human nutrition. Improving both the quantity and quality of cereal protein therefore represents a critical opportunity to enhance human health while reducing reliance on environmentally intensive animal-based foods. In this Review, we synthesize recent advances in understanding how grain protein content and composition are regulated in cereals, and why protein enhancement has historically been constrained by trade-offs with starch accumulation and yield. We discuss how domestication and modern breeding reshaped carbon and nitrogen allocation in cereal grains, creating a starch-dominant optimum that limits protein concentration. Drawing on genetic studies from rice, maize and wheat, we highlight emerging strategies that improve nitrogen acquisition, amino acid transport, storage protein composition and endosperm buffering capacity, enabling partial decoupling of protein accumulation from yield penalties. Finally, we place cereal protein biofortification within a broader nutritional and environmental context. Enhancing protein density and amino acid balance in staple cereals can improve dietary adequacy for vulnerable populations while lowering greenhouse gas emissions per unit of nutrition. Together, these insights position cereal protein biofortification as a scalable and equitable pathway towards healthier diets and more sustainable food systems under global climate and population pressures. Cereal protein biofortification can improve nutrition while maintaining yield and lowering environmental impact. This Review shows how genetics and breeding can enhance protein quality in staple cereals to support healthier and more sustainable diets.

In recent years, DNA engineering technology has undergone significant advancements, with CRISPR-based target-specific DNA insertion emerging as one of the most rapidly expanding and widely studied approaches. Traditional DNA insertion technologies employing recombinases typically involve introducing foreign DNA into genes in vivo by either pre-engineering recognition sequences specific to the recombinase or through genetic crossing to incorporate the requisite recognition sequence into the target gene. However, CRISPR-based gene insertion technologies have advanced to streamline this engineering process by combining the CRISPR–Cas module with recombinase enzymes. This process enables accurate and efficient one-step insertion of foreign DNA into the target gene in vivo. Here we provide an overview of the latest developments in CRISPR-based gene insertion technologies and discusses their potential future applications. As scientists work to understand complex traits and develop new therapies, they need tools to edit large sections of DNA. Traditional methods such as recombinases are constrained by their requirement for highly specific DNA sequence recognition, which limits their versatility and applicability. This study focuses on CRISPR systems, which use reprogrammed guide RNA for precise changes. However, CRISPR can create double-strand breaks, which can cause unintended changes. To address this, scientists are developing methods like prime editing, which makes precise edits without breaking both DNA strands. The study also highlights recent advances in CRISPR-based approaches for large-scale DNA integration. These methods show promise but need further refinement for use in human cells. Researchers conclude that while progress is being made, more work is needed to improve efficiency and reduce unintended effects. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Microbial utilization of methylamines (MAs) exerts profound effects on biogeochemical carbon cycles, yet the regulatory mechanisms enabling bacterial adaptation to fluctuating MAs availability remain elusive. Here, we report the discovery of previously unknown atypical response regulators, designated SecRs. They exhibit homology to RcsB from the two-component regulatory system but lack the conserved phosphorylation motif and a cognate kinase. SecRs serve as the gatekeeper of the serine cycle, an essential one-carbon assimilation pathway required for bacterial growth on MAs. Remarkably, Aminobacter sp. strain NyZ550 encodes both chromosomal and plasmid-borne secR homologs that differentially regulate identical targets encoding the serine cycle enzymes. Inactivation of secRs in strain NyZ550 abolishes its growth on MAs. Biochemical analyses demonstrate that purified SecRs form stable dimers capable of direct binding to the promoters of their own genes and those of the serine cycle genes, consequently activating transcription. SecR homologs are distributed among diverse terrestrial and marine methylotrophs, and frequently adjacent to the serine cycle genes in four distinct genomic arrangements, demonstrating that SecR-mediated regulation is conserved despite divergent evolutionary rearrangements of the serine cycle genes. The findings highlight the crucial role of SecR regulation in enabling microbial adaptation to biogeochemically important one-carbon compounds across diverse environments. Discovery of uncharacterized atypical response regulators (SecRs) lacking phosphorylation domains that directly activate the essential serine cycle, enabling microbial methylamine metabolism in widespread terrestrial and marine methylotrophs.