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The discovery and utilization of biocatalysts that selectively valorize lignocellulose is critical to the profitability of next-generation biorefineries. Here, we report the development of a refactored, whole-cell, GFP-based biosensor for high-throughput identification of biocatalysts that transform lignin into specialty chemicals from environmental DNA of uncultivable archaea and bacteria. The biosensor comprises the transcriptional regulator and promoter of the emrRAB operon of E. coli, and the configuration of the biosensor was tuned with the aid of mathematical model. The biosensor sensitively and selectively detects vanillin and syringaldehyde, and responds linearly over a wide detection range. We employed the biosensor to screen 42 520 fosmid clones comprising environmental DNA isolated from two coal beds and successfully identified 147 clones that transform hardwood kraft lignin to vanillin and syringaldehyde.

Most medications targeting optic neuropathies are administered as eye drops. However, their corneal penetration efficiencies are typically < 5%. There is a clear, unmet need for novel transcorneal drug delivery vehicles. To this end, we have developed a stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for controlled release of poorly bioavailable drugs into the aqueous humor of the eye. The hydrogel is formulated as a composite of hyaluronic acid (HA) and methylcellulose (MC). The amphiphilic nanoparticles are composed of poly(ethylene oxide) (PEO) and poly(lactic acid) (PLA). Experimental design aided the identification of hydrogel composition and nanoparticle content in the formulation, and the formulation reliably switched between thixotropy and temperature-dependent rheopexy when it was tested in a rheometer under conditions that simulate the ocular surface, including blinking. These properties should ensure that the formulation coats the cornea through blinking of the eyelid and facilitate application of the medication as an eye drop immediately prior to the patient’s bedtime. We subsequently tested the efficacy of our formulation in whole-eye experiments by loading the nanoparticles with cannabigerolic acid (CBGA). Our formulation exhibits over a 300% increase in transcorneal penetration over control formulations. This work paves the way for the introduction of novel products targeting ocular diseases to the market.

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