Polyketides represent an extremely diverse class of secondary metabolites often explored for their bioactive traits. These molecules are also attractive building blocks for chemical catalysis and polymerization. However, the use of polyketides in larger scale chemistry applications is stymied by limited titers and yields from both microbial and chemical production. Here, we demonstrate that an oleaginous organism (specifically, ) can overcome such production limitations owing to a natural propensity for high flux through acetyl-CoA. By exploring three distinct metabolic engineering strategies for acetyl-CoA precursor formation, we demonstrate that a previously uncharacterized pyruvate bypass pathway supports increased production of the polyketide triacetic acid lactone (TAL). Ultimately, we establish a strain capable of producing over 35% of the theoretical conversion yield to TAL in an unoptimized tube culture. This strain also obtained an averaged maximum titer of 35.9 ± 3.9 g/L with an achieved maximum specific productivity of 0.21 ± 0.03 g/L/h in bioreactor fermentation. Additionally, we illustrate that a β-oxidation-related overexpression () can support high TAL production and is capable of achieving over 43% of the theoretical conversion yield under nitrogen starvation in a test tube. Next, through use of this bioproduct, we demonstrate the utility of polyketides like TAL to modify commodity materials such as poly(epichlorohydrin), resulting in an increased molecular weight and shift in glass transition temperature. Collectively, these findings establish an engineering strategy enabling unprecedented production from a type III polyketide synthase as well as establish a route through O-functionalization for converting polyketides into new materials.

We present an improvement in the rate, utility, and mechanistic understanding of mono-μ-oxo-dialuminum initiators for epoxide ring-opening polymerization.

The ability to direct cell behavior has been central to the success of numerous therapeutics to regenerate tissue or facilitate device integration. Biomaterial scientists are challenged to understand and modulate the interactions of biomaterials with biological systems in order to achieve effective tissue repair. One key area of research investigates the use of extracellular matrix-derived ligands to target specific integrin interactions and induce cellular responses, such as increased cell migration, proliferation, and differentiation of mesenchymal stem cells. These integrin-targeting proteins and peptides have been implemented in a variety of different polymeric scaffolds and devices to enhance tissue regeneration and integration. This review first presents an overview of integrin-mediated cellular processes that have been identified in angiogenesis, wound healing, and bone regeneration. Then, research utilizing biomaterials are highlighted with integrin-targeting motifs as a means to direct these cellular processes to enhance tissue regeneration. In addition to providing improved materials for tissue repair and device integration, these innovative biomaterials provide new tools to probe the complex processes of tissue remodeling in order to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

Polymer topology dictates dynamic and mechanical properties of materials. For most polymers, topology is a static characteristic. In this article, we present a strategy to chemically trigger dynamic topology changes in polymers in response to a specific chemical stimulus. Starting with a dimerized PEG and hydrophobic linear materials, a lightly cross-linked polymer, and a cross-linked hydrogel, transformations into an amphiphilic linear polymer, lightly cross-linked and linear random copolymers, a cross-linked polymer, and three different hydrogel matrices were achieved via two controllable cross-linking reactions: reversible conjugate additions and thiol−disulfide exchange. Significantly, all the polymers, before or after topological changes, can be triggered to degrade into thiol-or amine-terminated small molecules. The controllable transformations of polymeric morphologies and their degradation herald a new generation of smart materials.

A combined theoretical and experimental investigation into the structure and mechanism of the classical Vandenberg catalyst for the isoselective polymerization of epoxides has led to a consistent mechanistic proposal. The most likely reaction pathway was based on a bis(μ-oxo)di(aluminum) (BOD) resting state that proceeded through a mono(μoxo)di(aluminum) (MOD) transition state. The isoselectivity of the Vandenberg catalyst was derived from the rigidity of the BOD structure and its bonding to the ultimate and penultimate oxygen heteroatoms along the polyether backbone. The energetic driving force for isoselectivity was the loss of an energetically favorable secondary Al−O interaction during enchainment of oppositely configured epoxides, providing a ca. 2 kcal/mol driving force for the emergent isoselectivity. Experimental spectroscopic and kinetic evidence based on model BOD and MOD complexes support the new mechanistic framework developed using density functional theory calculations. A purposefully synthesized BOD analogue of the proposed Vandenberg structure produced a characteristically isotactically enriched poly(allyl glycidyl ether) as produced by the classical Vandenberg catalyst. In situ 1 H NMR spectroscopy of a Vandenberg-catalyzed polymerization of allyl glycidyl ether revealed the activation enthalpy (ΔH ‡ = 21 kcal/mol) and energetics of epoxide−aluminum coordination (ΔH = −4.0 ± 1.0 kcal/mol, ΔS = −0.018 ± 0.004 kcal/(K mol)) by observation of the shifting acetylacetonate signal located on the active site of the Vandenberg catalyst in the 1 H NMR spectra of polymerization.

The uneven permeation of cations and anions through forward osmosis membranes offers a new technical challenge in the development of forward osmosis processes. Cation exchange in polyamide thin film composite membranes is caused by carboxylic acid functional groups within the structure of these membranes’ selective layers. These functional groups will gain or lose a proton depending on the external solution pH. The deprotonation of a polyamide at alkaline pHs results in a net negative charge, allowing for the exchange of cations between feed and draw solutions having monovalent cations. In this study, the importance of solution pH in influencing cation transport across a commercial thin film composite forward osmosis membrane was examined. It was found that cation transport across this membrane varies significantly with changes in pH and occurred fastest at alkaline pH.

No abstract

Copolymerization provides a modular strategy for compositional control of structure−property relationships in polymeric materials. However, this versatility is typically limited to structurally homologous comonomers. To further expand the scope of copolymerization in heterocyclic systems, we explored the copolymerization of structurally distinct lactones and epoxides utilizing the classical Vandenberg catalyst. Copolymerizations were conducted between monomer pairs selected from among two common lactones (DL-lactide, ε-caprolactone) and four epoxides (epichlorohydrin, butylene oxide, propylene oxide, ethylene oxide). The resultant materials had molecular weights of up to 16 Mg/mol. Reactivity ratios were determined for the copolymerization of DL-lactide and propylene oxide, which were consistent with a gradient copolymer with propylene oxide (PO) being the preferred monomer: r PO = 2.81 ± 0.27 and r LA = 0.36 ± 0.02. The copolymerization between ε-caprolactone and propylene oxide was also monitored by 1 H NMR spectroscopy. A greater preference for propylene oxide was evident, but incomplete consumption of the ε-caprolactone under these reaction conditions complicated determination of reactivity ratios. Meyer−Lowry analysis of the time-dependent compositional data provided estimates of r PO = 2.17 ± 0.04 and r CL = 0.08 ± 0.01. Distinct ester−ether dyad signals were observed in the 1 H NMR spectra of the copolymers, and thermal properties of the copolymers were distinct from those of the respective pure homopolymers. The expected hydrolytic degradability of poly[(DLlactide)-co-(ethylene oxide)] was demonstrated under neutral and basic conditions.