Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.07.02.184457

"Scentsor": A Whole-Cell Yeast Biosensor with an Olfactory Reporter for Low-Cost and Equipment-Free Detection of Pharmaceuticals

Miller, R. A.·Lee, S.·Fridmanski, E. J.·Barron, E.·Pence, J. T.·Lieberman, M.·Goodson, H. V.
View original source ↗Export metadata ↓

Abstract

Portable and inexpensive analytical tools are required to monitor pharmaceutical quality in technology limited settings including low- and middle-income countries (LMICs). Whole cell yeast biosensors have the potential to help meet this need. However, most of the read-outs for yeast biosensors require expensive equipment or reagents. To overcome this challenge, we have designed a yeast biosensor that produces a unique scent as a readout. This inducible scent biosensor, or "scentsor," does not require the user to administer additional reagents for reporter development and utilizes only the users nose to be "read." In this manuscript, we describe a scentsor that is responsive to the hormone estradiol (E2). The best estimate threshold (BET) for E2 detection with a panel of human volunteers (n = 49) is 39 nM E2 (15 nM when "non-smellers" are excluded). This concentration of E2 is sensitive enough to detect levels of E2 that would be found in dosage forms. This manuscript provides evidence that scent has potential for use in portable yeast biosensors as a read out, particularly for use in technology-limited environments.

Source connections

Explore related subjects

synthetic biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Miller, R. A., Lee, S., Fridmanski, E. J., Barron, E., Pence, J. T., Lieberman, M., Goodson, H. V.. 2020-07-03. "Scentsor": A Whole-Cell Yeast Biosensor with an Olfactory Reporter for Low-Cost and Equipment-Free Detection of Pharmaceuticals. https://doi.org/10.1101/2020.07.02.184457

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A High-Efficiency Geranylation Platform Enabled by Rational Tuning of a Single-Residue-Coded Chemo- and Regioselective Switch in Aromatic Prenyltransferases

Geranylation is an efficient post-modification strategy for enhancing or introducing new properties to molecules; however, achieving both high efficiency and precision remains challenging. Aromatic prenyltransferases (PTs) provide a mild and sustainable approach, yet their practical application is often limited by the trade-off between broad substrate scope and low selectivity, and successfully balancing these properties is rare. Here, using the pharmaceutically relevant cannabigerol framework as a model, we identify a single-residue switch in a prenyltransferase from Aspergillus terreus (AtaPT) that governs both chemo- and regioselectivity. Rational tuning of this switch preserves broad substrate scope while enhancing selectivity, enabling the selective formation of each of the three possible mono-geranylated products in the model reaction. Structural analysis reveals that this residue modulates the selectivity and activity through coupled steric and electrostatic effects. Notably, transplantation of this site into three homologous PTs similarly reprogrammed selectivity, establishing a conserved and generalizable control mechanism. Leveraging these insights, we achieved selective geranylation across 36 aromatic substrates, affording 41 products. Integration with an efficient geranyl donor regeneration system enabled preparative-scale synthesis, reaching titers up to 324 mg/L. This work defines a unifying mechanism for selectivity control in PTs and provides a high-efficiency platform for geranylation.

synthetic biology↗
bioRxiv2026

Programmable interphyla communication for Staphylococcus aureus by transferability of homoserine lactone sensors between Bacillales bacteria

Staphylococcus aureus is a Gram-positive opportunistic pathogen of the order Bacillales and a frequent member of human-associated microbiomes. Despite its clinical relevance, engineering S. aureus and the communities it inhabits remains limited by a shortage of well-characterized genetic tools for precise control of gene expression and intercellular signaling. Biosensors for homoserine lactones (HSLs) are widely used in Gram-negative bacteria, as HSLs are small, passively diffusible signaling molecules for and their sensors are tightly regulated. Here, we show that synthetically designed HSL sensors using LuxR-family regulators are highly functional in S. aureus. Notably, synthetic designs previously built for the Gram-positive model Bacillus subtilis, a distantly related Bacillales, transferred functionally and establish repurposing the genetic toolbox as an effective strategy for importing these functions into S. aureus. Sensor performance correlated strongly between the two Bacillales, and activation in S. aureus reached 55-fold, exceeding the dynamic range of reported inducible systems. We further demonstrate tightly regulated, programmable interphyla communication between Gram-negative Escherichia coli and S. aureus via HSL signaling. These results provide a new toolset for engineering interbacterial communication and open a route to extending programmable HSL signaling to other tough-to-engineer bacteria.

synthetic biology↗
bioRxiv2026

DIALECT: DNA-Programmable Synthetic Cells Communicate with Mammalian Cells through Synthetic Receptors

Synthetic cells can regulate mammalian signalling through the controlled release of diffusible protein ligands, but coupling programmable synthetic-cell senders to orthogonal, engineered mammalian receptors remains challenging. Here we present DIALECT (DNA-Instructed Assembly of Ligands for Engineered Cellular Transduction), a platform in which proteinosome-based synthetic cells translate sequence-defined DNA inputs into coiled-coil signalling ligand outputs for engineered mammalian receptors. DNA-ligand conjugates are localized within semipermeable proteinosomes through DNA hybridization and released by toehold-mediated DNA strand displacement (TMSD). The released ligands diffuse to neighbouring mammalian cells and activate cognate CC-GEMS receptors, inducing JAK/STAT3 signalling and reporter activation, with a higher response in cognate than non-cognate receiver cells under activation conditions. We further implement distributed Boolean AND logic using two independently programmed proteinosome populations that respond to distinct DNA inputs and release complementary ligand components. Simultaneous addition of both inputs produces substantially higher reporter activity than the respective single-input conditions, consistent with extracellular assembly of an active receptor agonist. DIALECT thus establishes a modular interface linking DNA-based molecular computation in synthetic cells to orthogonal signalling pathways in mammalian cells, providing a foundation for hybrid artificial-biological communication networks.

synthetic biology↗