{"title":"Discovery and development of penicillin-binding protein-type thioesterases as biocatalysts","authors":"Zachary L Budimir , Elizabeth I Parkinson","doi":"10.1016/j.copbio.2025.103417","DOIUrl":"10.1016/j.copbio.2025.103417","url":null,"abstract":"<div><div>Cyclic peptides are promising drug candidates, but their synthesis, especially the synthesis of small, strained rings, remains challenging. Penicillin-binding protein-type thioesterases (PBP-TEs) have emerged as versatile biocatalysts that catalyze head-to-tail macrocyclization of nonribosomal peptides. Unlike canonical thioesterase domains, which catalyze diverse offloading outcomes, PBP-TEs exclusively promote head-to-tail cyclization, offering predictable reactivity. Their ability to act on diverse substrates <em>in vitro</em> further underscores their potential as tools for peptide drug discovery. This review highlights PBP-TE discovery and substrate scope investigation, along with recent advances in structural characterization and engineering, establishing these enzymes as a promising platform for the biocatalytic synthesis of cyclic peptides.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103417"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unlocking therapeutic impacts of the gut microbiota with computational tools","authors":"Anjali Kharb , Xuejun Zhu","doi":"10.1016/j.copbio.2025.103431","DOIUrl":"10.1016/j.copbio.2025.103431","url":null,"abstract":"<div><div>The human gut microbiota, particularly the intestinal microbiota, shapes host physiology, disease risk, and therapeutic outcomes through complex metabolic and enzymatic activities. Recent advances in molecular omics, metabolomics, enzyme bioinformatics, and artificial intelligence (AI) have created unprecedented opportunities to elucidate its therapeutic roles to further enable precision microbiome medicine for personalized prevention, diagnosis, and treatment. In this review, we highlight emerging applications that leverage molecular omics and metabolomics technologies to dissect gut microbial functions, along with developments in enzyme bioinformatics and AI tools that reveal gut microbial species, enzymes, and metabolic pathways impacting human health. Finally, we discuss perspectives on data standardization, functional annotation, and interpretability, and how emerging tools are accelerating translational microbiome research.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103431"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetically pliable green algae for bioproduction of modified fatty acids, nutritional therapeutic oils, and biopharmaceuticals","authors":"Jeffrey L Moseley , Sabeeha S Merchant","doi":"10.1016/j.copbio.2025.103421","DOIUrl":"10.1016/j.copbio.2025.103421","url":null,"abstract":"<div><div>Homologous recombination (HR) is an essential tool for complex metabolic engineering in yeast, but transgene integration into plant and green algal nuclear genomes predominantly occurs by non-homologous end-joining. Species of the closely related, oleaginous trebouxiophytes <em>Auxenochlorella</em> and <em>Prototheca</em>, are unusual among the green algae in that HR is the favored mechanism for DNA integration into the nuclear genome. This property enables locus-specific targeting of gene cassettes encoding multiple enzymes for manipulating existing biochemical pathways or introducing new functions. Genetic malleability, and regulatory approval for human consumption, coupled with robust fermentation performance at industrial scale, establishes <em>Auxenochlorella</em> and <em>Prototheca</em> as prime candidates for algal production of biochemicals and biomaterials. The examples presented here highlight strain improvement and engineering for synthesis of hydroxylated fatty acids for biomaterials, structured triglycerides resembling human milk fat for infant nutrition, very-long-chain mono- and polyunsaturated fatty acids with nutraceutical or therapeutic potential, and cannabinoids for pharmacological applications.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103421"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional cereal pan-genomics: harnessing structural and regulatory variation for precision crop design","authors":"Zihao Zhu , Srijan Jhingan , Erwang Chen , Nils Stein","doi":"10.1016/j.copbio.2025.103418","DOIUrl":"10.1016/j.copbio.2025.103418","url":null,"abstract":"<div><div>Cereal pan-genomics, powered by long-read sequencing and multi-omics integration, provides high-resolution maps of structural variants, regulatory elements, and adaptive alleles across cultivated and wild germplasm. Here, we review how these comprehensive resources uncover trait-associated variation inaccessible to single-reference approaches, enabling haplotype-informed breeding, pathway engineering, and targeted introgression of wild alleles. Integration with regulatory genomics — the study of noncoding elements controlling gene expression — and 3D genome architecture further enables precision editing of noncoding elements for phenotypic fine-tuning. Together, these advances position cereal pan-genomics as a foundational platform for predictive crop design, accelerating the development of high-yielding, climate-resilient varieties while providing actionable guidance for breeding strategies.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103418"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryan Palaganas , Dimitrios N Sidiropoulos , Meaghan Morris , Genevieve L Stein-O’Brien
{"title":"Mapping multipathology via spatial omic integration","authors":"Ryan Palaganas , Dimitrios N Sidiropoulos , Meaghan Morris , Genevieve L Stein-O’Brien","doi":"10.1016/j.copbio.2025.103398","DOIUrl":"10.1016/j.copbio.2025.103398","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDDs) are a global health crisis affecting 15% of the population, with projections indicating this burden will double within two decades. Despite having shared molecular hallmarks, co-occurring proteinopathies, predictable progression patterns, and overlapping genetic risk variants, what causes specific NDDs to manifest in a particular individual or even a particular cell type is unknown. Thus, systems biology approaches are necessary to decipher the molecular, cellular, and environmental interactions driving pathogenesis. Multi-omics spatial profiling preserves tissue architecture while mapping cellular phenotypes and molecular interactions at subcellular resolution. Systems biology integration of these modalities will facilitate the identification of underlying causes of neuronal vulnerability, protein aggregation mechanisms, and disease progression patterns, accelerating targeted therapeutic development across NDDs.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103398"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expanding the catalytic repertoire of C–C bond–forming pyridoxal 5′-phosphate-dependent enzymes for noncanonical amino acid formation","authors":"Taku Mizutani , Ikuro Abe","doi":"10.1016/j.copbio.2026.103437","DOIUrl":"10.1016/j.copbio.2026.103437","url":null,"abstract":"<div><div>Noncanonical amino acids (ncAAs) are pharmaceutically important molecules with diverse biological and chemical applications. Among various production strategies, biocatalytic synthesis using pyridoxal 5′-phosphate (PLP)-dependent enzymes has attracted considerable attention owing to their high stereoselectivity and versatility in forming new C–C bonds. Recent advances in enzyme engineering have further expanded the catalytic potential of PLP-dependent enzymes, enabling the tailored synthesis of target ncAAs. In this short review, we summarize recent developments in biocatalytic ncAA synthesis achieved through engineered PLP-dependent enzymes.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103437"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julian Elijah Politsch , Alberto González-Delgado , Krzysztof Wabnik
{"title":"From big data to mechanistic insights: decoding plant complexity with models","authors":"Julian Elijah Politsch , Alberto González-Delgado , Krzysztof Wabnik","doi":"10.1016/j.copbio.2025.103428","DOIUrl":"10.1016/j.copbio.2025.103428","url":null,"abstract":"<div><div>Recent advances in high-throughput sequencing, imaging, and phenotyping have carried plant science into the era of ‘big data.’ Complex, multi-scale datasets provide new opportunities to uncover plant molecular mechanisms with a level of detail previously unachievable. Fully exploiting this complexity requires integrating advanced statistics, computational modeling, and artificial intelligence (AI). This minireview offers guidance on how the combination of AI and mechanistic models is transforming temporal, image-based, and spatial omics data into detailed predictions of robust plant traits. In addition, embedding physical principles into AI models can enhance interpretability and strengthen their biological grounding, leading to more realistic representations of plant inner workings. Together, these advances are reshaping plant science by turning ‘big data’ into deep insights, thus greatly enriching our understanding of plant growth, adaptation, and environmental responses.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103428"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruno Pok Man Ngou , Yasuhiro Kadota , Ken Shirasu
{"title":"A guide to designing cell-surface receptors in plants","authors":"Bruno Pok Man Ngou , Yasuhiro Kadota , Ken Shirasu","doi":"10.1016/j.copbio.2025.103420","DOIUrl":"10.1016/j.copbio.2025.103420","url":null,"abstract":"<div><div>Cell-surface receptors perceive environmental cues and trigger appropriate responses. In plants, these receptors comprise ectodomain, juxta-membrane, and cytosolic regions that define ligand specificity, modulate co-receptor associations, and fine-tune downstream signaling, respectively. Here we highlight the mechanistic principles underlying each module and discuss strategies to reprogram them. By integrating structural insights with illustrative examples, we provide a blueprint for designing cell-surface receptors with customized recognition specificity and programmable outputs, offering new opportunities to enhance plant resilience in the face of rapid climate change.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103420"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claudia Beraldo, Alessandro Alboresi, Tomas Morosinotto
{"title":"Photoprotective-based strategies to enhance crop yield under fluctuating light conditions","authors":"Claudia Beraldo, Alessandro Alboresi, Tomas Morosinotto","doi":"10.1016/j.copbio.2025.103424","DOIUrl":"10.1016/j.copbio.2025.103424","url":null,"abstract":"<div><div>Photosynthesis is a fundamental biological process, and optimizing its efficiency is crucial for increasing crop yields without expanding cultivated land. Photosynthesis is finely regulated, and plants employ photoprotective mechanisms such as non-photochemical quenching (NPQ) and alternative electron pathways to dissipate excess energy and avoid potential damage.</div><div>In field conditions, light availability fluctuates rapidly due to environmental variability and canopy architecture, creating alternating periods of saturating illumination and shade, a context where photoprotection mechanisms are essential but also generate energy losses. Promising improvements in light-use efficiency have been obtained by optimizing NPQ response to field conditions, though impacts vary across species. These results highlight the need for strategies tailored to species and environment and for exploration of complementary approaches targeting other mechanisms.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103424"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Strategies and challenges for synthetic apomixis","authors":"Hui Ren , Venkatesan Sundaresan","doi":"10.1016/j.copbio.2025.103433","DOIUrl":"10.1016/j.copbio.2025.103433","url":null,"abstract":"<div><div>Harnessing heterosis has been important to agriculture, but its full potential remains constrained by the inability to clonally propagate hybrid seeds. Synthetic apomixis, engineering asexual seed formation in sexual crops, provides a path to fix heterosis through generations. This review compiles current advances in engineering synthetic apomixis, focusing on two major components: the substitution of mitosis for meiotic divisions and maternally derived embryo development by haploid inducer or parthenogenesis. Despite rapid progress made in rice, significant challenges remain for general implementation and extension to other crops. We discuss these challenges and the possible paths forward to make synthetic apomixis feasible for widespread application in agriculture.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103433"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}