SynBio, Volume 4, Issue 3 (September 2026) – 3 articles

Industrial bioprocesses remain constrained by their limited ability to monitor intracellular events in real time. Most rely on external measurements—nutrient or metabolite levels in the culture medium—that provide only delayed and indirect information about the cell’s internal state. Riboswitches, RNA elements that respond to specific small molecules, offer a complementary route to direct intracellular sensing. Acting as genetically encoded biosensors, they bind metabolites with nanomolar-to-micromolar affinity, and ligand binding drives rapid conformational changes in the RNA. When coupled to gene regulatory outputs, riboswitches can, in principle, support dynamic feedback control that allows cells to sense metabolic imbalances and adjust their own metabolism. This Commentary argues that the central opportunity is conceptual: reframing intracellular biosensing as a foundational layer for adaptive, self-regulating cell factories. It distinguishes what riboswitch technology already demonstrates at laboratory scale from what remains a forward-looking vision, and outlines the engineering barriers, specificity, dynamic range, context-dependence, metabolic burden, evolutionary stability, and validation in production settings that must be addressed before autonomous bioprocess control becomes routine. Importantly, the functional response time of such systems is governed not by binding kinetics alone but by transcription, translation and mRNA turnover, a distinction that matters for feedback stability. Full article

The production of multiple proteins using a single open reading frame (sORF)/polyprotein system is a powerful strategy for coordinated multi-protein expression in eukaryotes. The most widely used approach relies on 2A peptides, but conventional 2A systems suffer from several limitations, and their viral origin makes them less than ideal for commercial crop biotechnology applications. Self-excising protein (SEP) modules are a promising alternative that enables coordinated production of multiple proteins from a single ORF encoding a polyprotein precursor. SEPs provide distinct advantages over conventional systems and effectively address many of the limitations inherent to the 2A approach. An SEP module is a fusion protein composed of an N-terminal excising domain (NED) and a C-terminal excising domain (CED) joined by a peptide linker. Using this architecture, a panel of SEP modules has been developed by pairing an engineered intein (serving as the NED) with various CEDs, including a second engineered intein, a 2A-like peptide, and ubiquitin. These modules release multiple proteins from the polyprotein precursor with nearly stoichiometric expression and clean cleavage. Coordinated coexpression using SEPs has been successfully demonstrated in several eukaryotic systems, including yeast, mammalian cells, and plants. This review offers a comprehensive analysis of the SEP technology while underscoring its major applications. Full article

Many species of actinomycete bacteria synthesise glycosylated polyene macrolides that have potential as antifungal drugs. The sugar residues of these compounds have profound effects on potency, toxicity and water-solubility. The medically important antibiotics amphotericin B and nystatin A1 have a single D-mycosamine sugar on C19 of the polyene macrolactone. A few naturally occurring polyenes have a second sugar residue. This may be attached to C35 of 38-membered macrolactones like nystatins or to the equivalent C27 of 30-membered pentaenes like selvamicin. The recently discovered mandimycin has a C35 disaccharide that changes the mode of action, reduces adverse side effects, and delays the emergence of resistance in laboratory cultures of fungal pathogens. Glycosyltransferases that can modify the C27 and C35 positions are of interest to synthetic biologists. The GloSV enzyme is predicted to add a 2,6-dideoxy-D-hexose to C27 of a pentaene in Saccharopolyspora gloriosae. Here we assess GloSV in strains of the amphotericin producer, Streptomyces nodosus. Low levels of new amphotericin analogues modified with D-oliose or D-digitoxose were identified through HR-LCMS. The identification of this glycosyltransferase will assist the development of streptomycete systems for production of non-toxic polyene glycoanalogues. Full article