Ester Side Chain Research Articles

A Machine Learning Model for Predicting the Propagation Rate Coefficient in Free-Radical Polymerization.

The propagation rate coefficient (kp) is one of the most crucial kinetic parameters in free-radical polymerization (FRP) as it directly governs the rate of polymerization and the resulting molecular weight distribution. The kp in FRP can typically be obtained through experimental measurements or quantum chemical calculations, both of which can be time consuming and resource intensive. Herein, we developed a machine learning model based solely on the structural features of monomers involved in FRP, utilizing molecular embedding and a Lasso regression algorithm to predict kp more efficiently and accurately. The result shows that the model achieves a mean absolute percentage error (MAPE) of only 5.49% in the predictions for four new monomers, which indicates that the model exhibits strong generalization capabilities and provides reliable and robust predictions. In addition, this model can accurately predict the influence of the ester side chain length of (meth)acrylates on kp, aligning well with established scientific knowledge. This approach offers a straightforward and practical model for other researchers to rapidly obtain accurate kp values by employing monomer structural information. The model is sufficiently general to apply to a wide range of (meth)acrylate and butadiene FRP monomers, thereby supporting kinetic modeling of polymerization reactions.

An Expedient Route to Bio‐based Polyacrylate Alternatives with Inherent Degradation Capabilities by Organic Catalysis for Polymerization of Muconate Esters

The quest for polymers that would be at the same time bio‐based and degradable after usage, in addition to offering chemical post‐modification options, remains a daunting challenge in contemporary polymer science. Despite advances in polymer chemistry, attempts at controlling the chain‐growth polymerization of muconate esters remain unexplored. Here we show that dialkyl muconates can be rapidly polymerized by organocatalyzed group transfer polymerization (O‐GTP). O‐GTP is conducted to completion at room temperature in toluene within a few minutes, using 1‐ethoxy‐1‐(trimethylsiloxy)‐1,3‐butadiene (ETSB) as initiator and 1‐tert‐butyl‐4,4,4‐tris(dimethylamino)‐2,2‐bis[tris(dimethylamino)‐phosphoranylidenamino]‐25,45 catenadi(phosphazene) (P4‐t­‐Bu) as catalyst. Chain extension experiments and synthesis of all muconate‐type block copolymers can also be achieved. Furthermore, polymuconates are amenable to facile post‐polymerization modification reactions. This is showcased through the hydrolysis of the ester side chains leading to well‐defined poly(muconic acid), and by epoxidation of the C=C double bonds of the main chain. Last but not least, these internal alkene groups can be selectively cleaved by ozonolysis, demonstrating the upcyclability of polymuconates under oxidative conditions. This work demonstrates that polymuconates constitute a unique platform of bio‐based polymers, easily modifiable in addition to being chemically degradable under user friendly experimental conditions.

An Expedient Route to Bio-Based Polyacrylate Alternatives with Inherent Post-Chemical Modification and Degradation Capabilities by Organic Catalysis for Polymerization of Muconate Esters.

The quest for polymers that would be at the same time bio-based and degradable after usage, in addition to offering chemical post-modification options, remains a daunting challenge in contemporary polymer science. Despite advances in polymer chemistry, attempts at controlling the chain-growth polymerization of muconate esters remain unexplored. Here we show that dialkyl muconates can be rapidly polymerized by organocatalyzed group transfer polymerization (O-GTP). O-GTP is conducted to completion at room temperature in toluene within a few minutes, using 1-ethoxy-1-(trimethylsiloxy)-1,3-butadiene (ETSB) as initiator and 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)-phosphoranylidenamino]-2 5,4 5 catenadi(phosphazene) (P4-t-Bu) as catalyst. Chain extension experiments and synthesis of all muconate-type block copolymers can also be achieved. Furthermore, polymuconates are amenable to facile post-polymerization modification reactions. This is showcased through the hydrolysis of the ester side chains leading to well-defined poly(muconic acid), and by epoxidation of the C=C double bonds of the main chain. Last but not least, these internal alkene groups can be selectively cleaved by ozonolysis, demonstrating the upcyclability of polymuconates under oxidative conditions. This work demonstrates that polymuconates constitute a unique platform of bio-based polymers, easily modifiable in addition to being chemically degradable under user friendly experimental conditions.

A comparative study of mechanical crushing and pyrolysis techniques for separation and recovery of discarded polycrystalline silicon photovoltaic modules

With the rapid growth of the photovoltaic (PV) industry, efficient recovery and utilization of discarded polycrystalline silicon PV modules have attracted increasing attention. This study compares the application of mechanical crushing and pyrolysis techniques in the recovery of PV modules. The results indicate that while mechanical crushing can preliminarily disintegrate materials, its effectiveness in separating valuable materials such as silver and aluminum is limited, particularly for particles larger than 1 mm. In contrast, pyrolysis techniques demonstrate outstanding performance in removing organic matter and separating silicon wafers and glass, notably enhancing the recovery rate of large glass particles. However, the brittleness of silicon wafers presents a challenge during pyrolysis. Furthermore, the pyrolysis mechanisms of ethylene-vinyl acetate (EVA) film and backsheet materials are thoroughly discussed. The pyrolysis process of EVA film involves two stages: firstly, the preferential decomposition of acetyl oxygens on ester side chains, followed by further pyrolysis decomposition of the main chain and side chains to generate alkanes. Pyrolysis of polyethylene terephthalate (PET) begins with the generation of methyl and benzoyl radicals, while polyvinyl fluoride (PVF) and polyvinylidene fluoride (PVDF) pyrolysis initiates with the detachment of head-group units, followed by sequential detachment of chain units. Given the advantages of pyrolysis techniques, this study recommends them as the preferred method for PV module recovery.

Ester Side Chain Functionalization Enhances Mechanical Properties of Poly(3-Hexylthiophene) while Maintaining High Hole Mobility

Ester Side Chain Functionalization Enhances Mechanical Properties of Poly(3-Hexylthiophene) while Maintaining High Hole Mobility

Interaction of Cyclodextrins with Amphiphilic Alternating Cooligomers Possessing the Dense Triazole Backbone.

The interaction of cyclodextrins (CDs) with structure-controlled polymers is expected to provide significant insights into macromolecular recognition. However, the interaction of CDs with structure-controlled polymers has been an underexamined issue of investigation. Herein, alternating amphiphilic cooligomers (oligoCnAH, where n denotes the carbon number of alkyl groups; n = 4, 8, and 12) were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition polymerization of heterodimers of 4-azido-5-hexynoic acid (AH) derivatives carrying N-alkylamide and t-butyl (tBu) ester side chains, followed by hydrolysis of the tBu ester, to study the interaction of CDs with oligoCnAH by 1H NMR, nuclear Overhauser effect spectroscopy, and pulse-field-gradient spin-echo NMR. These NMR studies indicated that αCD interacted with oligoC4AH, αCD and βCD interacted with oligoC8AH, and all CDs interacted with oligoC12AH. Based on the equilibrium models proposed, the binding constants were evaluated for the binary mixtures, which showed interaction. Comparing the interactions of the CDs/oligoC12AH binary mixtures with those of the binary mixtures of CDs and alternating copolymers of sodium maleate and dodecyl vinyl ether (polyC12M), it is concluded that oligoC12AH forms less stable micelles than does polyC12M presumably because of the lower molecular weight, the hydrophilic amide groups in the side chain, and the longer interval between neighboring C12 groups in oligoC12AH.

Enantioselective Self‐Assembly of a Homochiral Tetrahedral Cage Comprising Only Achiral Precursors

AbstractHow Nature synthesizes enantiomerically pure substances from achiral or racemic resources remains a mystery. In this study, we aimed to emulate this natural phenomenon by constructing chiral tetrahedral cages through self‐assembly, achieved by condensing two achiral compounds–a trisamine and a trisaldehyde. The occurrence of intercomponent CH⋅⋅⋅π interactions among the phenyl building blocks within the cage frameworks results in twisted conformations, imparting planar chirality to the tetrahedrons. In instances where the trisaldehyde precursor features electron‐withdrawing ester side chains, we observed that the intermolecular CH⋅⋅⋅π forces are strong enough to prevent racemization. To attain enantioselective self‐assembly, a chiral amine was introduced during the imine formation process. The addition of three equivalents of chiral amino mediator to one equivalent of the achiral trisaldehyde precursor formed a trisimino intermediate. This chiral compound was subsequently combined with the achiral trisamino precursor, leading to an imine exchange reaction that releasing the chiral amino mediator and formation of the tetrahedral cage with an enantiomeric excess (ee) of up to 75 %, exclusively composed of achiral building blocks. This experimental observation aligns with theoretical calculations based on the free energies of related cage structures. Moreover, since the chiral amine was not consumed during the imine exchange cycle, it enabled the enantioselective self‐assembly of the tetrahedral cage for multiple cycles when new batches of the achiral trisaldehyde and trisamino precursors were successively added.

Enantioselective Self-Assembly of a Homochiral Tetrahedral Cage Comprising Only Achiral Precursors.

How Nature synthesizes enantiomerically pure substances from achiral or racemic resources remains a mystery. In this study, we aimed to emulate this natural phenomenon by constructing chiral tetrahedral cages through self-assembly, achieved by condensing two achiral compounds-a trisamine and a trisaldehyde. The occurrence of intercomponent CH⋅⋅⋅π interactions among the phenyl building blocks within the cage frameworks results in twisted conformations, imparting planar chirality to the tetrahedrons. In instances where the trisaldehyde precursor features electron-withdrawing ester side chains, we observed that the intermolecular CH⋅⋅⋅π forces are strong enough to prevent racemization. To attain enantioselective self-assembly, a chiral amine was introduced during the imine formation process. The addition of three equivalents of chiral amino mediator to one equivalent of the achiral trisaldehyde precursor formed a trisimino intermediate. This chiral compound was subsequently combined with the achiral trisamino precursor, leading to an imine exchange reaction that releasing the chiral amino mediator and formation of the tetrahedral cage with an enantiomeric excess (ee) of up to 75 %, exclusively composed of achiral building blocks. This experimental observation aligns with theoretical calculations based on the free energies of related cage structures. Moreover, since the chiral amine was not consumed during the imine exchange cycle, it enabled the enantioselective self-assembly of the tetrahedral cage for multiple cycles when new batches of the achiral trisaldehyde and trisamino precursors were successively added.

Enhancing lathyrane structural diversity and MDR activity by combinatorial modification of lathyrane nucleus and ester side chain: A case study of Euphorbia Factor L1 and Euphorbia Factor L3

The chemical transformation of lathyrane nucleus through reduction and oxidation reactions using Euphorbia Factor L1 (EFL1) and Euphorbia Factor L1 (EFL3) as examples were investigated, along with a co-modification strategy of lathyrane nucleus and its side ester chain. A total of 38 lathyrane derivatives (5–42) including 34 new compounds were obtained, which greatly enriched the structural diversity of the lathyrane-type diterpenoids. Cytotoxicity against drug-sensitive and drug (adriamycin, ADM) resistant MCF-7 cells showed that 23 out of 38 transformed derivatives possessed obvious cytotoxic activity with IC50 values ranging from 7.0 to 41.1 μM and 3.2 to 45.5 μM, respectively, against both cells, compared to the noncytotoxic EFL1 and EFL3. The multidrug resistance (MDR) reversing activities of these lathyrane derivatives were further evaluated in MCF-7/ADM. Three transformed compounds (reversal fold, RF = 151.33, 62.94 and 47.3 for 27, 37 and 42) showed markedly higher activity than EFL1 (RF = 32.92) and EFL3 (RF = 39.68). Structure-activity relationship study revealed an essential role of C-6/17 and C-12/13 double bonds on lathyrane nucleus for exerting MDR reversal activity. Western blotting analysis showed that 42 could reduce the expression level of P-glycoprotein (P-gp) in MCF-7/ADM cells; however, the most active compound 27 with an unnatural 5/7/7/4 fused-ring diterpenoid skeleton, had no inhibitory effect on P-gp expression.

Suzuki–Miyaura Catalyst-Transfer Condensation Polymerization for the Synthesis of Polyphenylene with Ester Side Chain by Using Stable, Reactive 1,1,2,2-Tetraethylethylene Glycol Boronate (B(Epin)) Monomer

Suzuki–Miyaura Catalyst-Transfer Condensation Polymerization for the Synthesis of Polyphenylene with Ester Side Chain by Using Stable, Reactive 1,1,2,2-Tetraethylethylene Glycol Boronate (B(Epin)) Monomer

Exploring the potential of a new marine bacterium associated with plastisphere to metabolize dibutyl phthalate and bis(2-ethylhexyl) phthalate by enrichment cultures combined with multi-omics analysis

Phthalic acid esters (PAEs) plasticizers are virulent endocrine disruptors that are mixed into plastics while fabricating and can filter out once they release into the surrounding environments. Plastic surfaces serve as new habitats for microorganisms, referred to as ‘plastisphere’. Previous metagenomic investigations of the ‘plastisphere’ indicated that marine plastic surfaces may harbor microbes that degrade PAEs plasticizers. To our knowledge, the potential of microorganisms in the marine ‘plastisphere’ to metabolize PAEs is poorly understood. In this study, by screening the natural microbial community on plastic debris that had been deployed in situ for up to 20 months, a novel marine bacterium, Microbacterium esteraromaticum DEHP-1, was successfully isolated, which could degrade and mineralize 10–200 mg/L dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP). According to the results of gas chromatography-mass spectrometry (GC-MS) and whole genome mining of strain DEHP-1, we found that strain DEHP-1 may metabolize DBP by successive removal of the ester side chain by esterase 2518 to produce mono-butyl phthalate (MBP) and phthalic acid (PA), whereas the degradation of DEHP may take place by the direct action of monooxygenase 0132 on the fatty acid side chain of the DEHP molecule to produce di-n-hexyl phthalate (DnHP) and DBP, and then the subsequent hydrolysis of DBP by de-esterification to PA and finally into the tricarboxylic acid (TCA) cycle. Non-targeted metabolomics results showed that intracellular degradation of PAEs did not happen. However, exposure to PAEs was found to significantly affect pathways such as arginine and proline, riboflavin, glutathione and lysine degradation. Therefore, the intracellular metabolic behavior of strain DEHP-1 exposed to PAEs was proposed for the first time. This study sheds light on the metabolic capacity and strategies of bacteria in the marine ‘plastisphere’ to effectively degrade PAEs and highlights the importance of marine microbes in mitigating plastic poisonousness.

Electrosynthesis of buckyballs with fused-ring systems from PCBM and its analogue

[6,6]-Phenyl-C61-butyric acid methyl ester (PCBM), a star molecule in the fullerene field, has found wide applications in materials science. Herein, electrosynthesis of buckyballs with fused-ring systems has been achieved through radical α-C−H functionalization of the side-chain ester for both PCBM and its analogue, [6,6]-phenyl-C61-propionic acid methyl ester (PCPM), in the presence of a trace amount of oxygen. Two classes of buckyballs with fused bi- and tricyclic carbocycles have been electrochemically synthesized. Furthermore, an unknown type of a bisfulleroid with two tethered [6,6]-open orifices can also be efficiently generated from PCPM. All three types of products have been confirmed by single-crystal X-ray crystallography. A representative intramolecularly annulated isomer of PCBM has been applied as an additive to inverted planar perovskite solar cells and boosted a significant enhancement of power conversion efficiency from 15.83% to 17.67%.

End Group Engineering for Constructing A-D-A Fused-Ring Photosensitizers with Balanced Phototheranostics Performance.

Phototheranostics continues to flourish in cancer treatment. Due to the competitive relationships between these photophysical processes of fluorescence emission, photothermal conversion, and photodynamic action, it is critical to balance them through subtle photosensitizer designs. Herein, it is provided a useful guideline for constructing A-D-A photosensitizers with superior phototheranostics performance. Various cyanoacetate group-modified end groups containing ester side chains of different length are designed to construct a series of A-D-A photosensitizers (F8CA1 ∼ F8CA4) to study the structure-property relationships. It is surprising to find that the photophysical properties of A-D-A photosensitizers can be precisely regulated by these tiny structural changes. The results reveal that the increase in the steric hindrance of ester side chains has positive impacts on their photothermal conversion capabilities, but adverse impacts on the fluorescence emission and photodynamic activities. Notably, these tiny structural changes lead to their different aggregation behavior. The molecule mechanisms are detailedly explained by theoretical calculations. Finally, F8CA2 nanoparticles with more balanced photophysical properties perform well in fluorescence imaging-guided photothermal and type I&II photodynamic synergistic cancer therapy, even under hypoxic conditions. Therefore, this work provides a novel practicable construction strategy for desired A-D-A photosensitizers.

Tetrathiophene-based fully non-fused ring electron acceptors via asymmetric side chain engineering

Side-chain engineering has been considered as one of the most promising strategies to optimize non-fullerene acceptors. In this work, we use side-chain engineering to synthesize three fully non-fused electron acceptors (FNEAs) i.e. two symmetric acceptors (4T-BE and 4T-TO) and one asymmetric acceptor (4T-BOE) by different side chain combination onto the tetrathiophene unit, which could effectively tune the molecular conformations, electronic properties, charge carrier transport, film morphology, and photovoltaic properties. From 4T-BE to 4T-BOE and 4T-TO, the molecules present more red-shifted absorption, smaller optical bandgaps, initially rising and then declining LUMO energy levels and stronger intermolecular stacking. When blended with polymer donor PBDB-T, asymmetric 4T-BOE with alkoxy and ester side chains demonstrate a champion PCE of 9.57% with a short-circuit current density (Jsc) of 16.28 mA/cm2, an open circuit voltage (Voc) of 0.87 V, and a fill factor (FF) of 67.50%, which was higher than that of the devices based on PBDB-T:4T-BE and PBDB-T:4T-TO. These results demonstrate that asymmetric side-chain engineering is an especially crucial and effective approach for the design of highly efficient FNEAs.

Synthesis of an alternating copolymer of the dense 1,2,3‐triazole backbone carrying t‐butyl ester and nitrile side chains

AbstractIn these decades, synthesis of polymers with controlled monomer sequences has been of increasing importance in polymer chemistry. When we tested synthesis of a heterodimer of 4‐azido‐5‐hexynoic acid derivatives carrying t‐butyl (tBu) ester and tBu amide side chains for preparation of an alternating copolymer, we unexpectedly obtained a heterodimer precursor carrying tBu ester and nitrile side chains, in a high yield. Since dense 1,2,3‐triazole polymers carrying nitrile side chains are expected as a new functional polymer, the heterodimer is polymerized by copper(I)‐catalyzed azide–alkyne cycloaddition polymerization to obtain an alternating copolymer carrying tBu ester and nitrile side chains in this study. Since 1,2,3‐triazole and nitrile moieties are known to be ligands for metal ions, the complex formation of the alternating copolymer with PdCl2 is also investigated by NMR. In the presence of PdCl2, 1H NMR spectra show broad and separated signals due to the free and complexed copolymers, indicative of slow exchange. Pulse‐field‐gradient spin‐echo NMR data indicated that the coordination of alternating copolymer to PdCl2 made the copolymer chains take a more compact conformation under dilute conditions. The density functional theory calculations indicated that the alternating copolymer coordinated to PdCl2 preferentially through the 1,2,3‐triazole nitrogen and nitrile nitrogen atoms.

Mannose-Decorated Co-Polymer Facilitates Controlled Release of Butyrate to Accelerate Chronic Wound Healing.

Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to realize clinical potential. Here, a novel polymeric delivery platform for tunable and sustainable release of butyrate consisting of a methacrylamide backbone with butyryl ester or phenyl ester side chains as well as mannosyl side chains, which is also applicable to other therapeutically relevant metabolites is reported. This platform's utility in the treatment of non-healing diabetic wounds is explored. This butyrate-containing material modulated immune cell activation in vitro and induced striking changes in the milieu of soluble cytokine and chemokine signals present within the diabetic wound microenvironment in vivo. This novel therapy shows efficacy in the treatment of non-healing wounds through the modulation of the soluble signals present within the wound, and importantly accommodates the critical temporal regulation associated with the wound healing process. Currently, the few therapies to address non-healing wounds demonstrate limited efficacy. This novel platform is positioned to address this large unmet clinical need and improve the closure of otherwise non-healing wounds.

Explosives removal and quantification using porous adsorbents based on poly(2-oxazoline)s with various degree of functionalization

Polymeric porous adsorbents are reported for removal of explosives, namely picric acid, 1,3,5-trinitro-1,3,5-triazinane (RDX), and pentaerythritol tetranitrate (PETN) and their subsequent quantification using direct analysis with ambient plasma mass spectrometry. The adsorbents are obtained by functionalization of short-chain poly(2-oxazoline)s with methyl ester side chains using 4-(aminomethyl)pyridine with a degree of functionalization equal to 0, 5, 10, and 20%. The subsequent step consist of cross-linking using a high internal phase emulsion procedure by further side-chain amidation with diethylenetriamine as crosslinker. Picric acid, RDX, and PETN were chosen as the model compounds as they belong to three different groups of explosives, in particular nitroaromatics, nitroamines, and nitrate esters, respectively. The adsorption isotherms, kinetics, as well as the influence of pH and temperature on the adsorption process was investigated. The porous adsorbents showed the highest maximum adsorption capacity towards picric acid, reaching 334 mg g−1, while PETN (80 mg g−1) and RDX (17.4 mg g−1) were less efficiently adsorbed. Subsequent quantification of the adsorbed explosives is performed by a specially designed ambient mass spectrometry setup equipped with a thermal heater. The obtained limits of detection were found to be 20-times improved compared to direct analysis of analyte solutions. The effectiveness of the proposed analytical setup is confirmed by successful quantification of the explosives in river water samples. The research clearly shows that functional porous adsorbents coupled directly with ambient mass spectrometry can be used for rapid quantification of explosives, which can be, e.g., used for tracking illegal manufacturing sites of these compounds.

Degradation of Polyacrylates by One-Pot Sequential Dehydrodecarboxylation and Ozonolysis

We establish a synthetically convenient method to degrade polyacrylate homopolymers. Carboxylic acids are installed along the polymer backbone by partial hydrolysis of the ester side chains, and then, in a one-pot sequential procedure, the carboxylic acids are converted into alkenes and oxidatively cleaved. This process enables the robustness and properties of polyacrylates to be maintained during their usable lifetime. The ability to tune the degree of degradation was demonstrated by varying the carboxylic acid content of the polymers. This method is compatible with a wide range of polymers prepared from vinyl monomers through copolymerization of acrylic acid with different monomers including acrylates, acrylamides, and styrenics.

Programmed Iteration Controls the Assembly of the Nonanoic Acid Side Chain of the Antibiotic Mupirocin.

Mupirocin is a clinically important antibiotic produced by Pseudomonas fluorescens NCIMB 10586 that is assembled by a complex trans-AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown. Herein we report the application of NMR spectroscopy, mass spectrometry, chemical probes and in vitro assays to establish the remaining steps of 9HN biosynthesis. These investigations reveal a complex interplay between a novel iterative or "stuttering" KS-AT didomain (MmpF), the multidomain module MmpB and multiple ACPs. This work has important implications for understanding the late-stage biosynthetic steps of mupirocin and will be important for future engineering of related trans-AT biosynthetic pathways (e.g. thiomarinol).

Programmed Iteration Controls the Assembly of the Nonanoic Acid Side Chain of the Antibiotic Mupirocin.

Mupirocin is a clinically important antibiotic produced by Pseudomonas fluorescens NCIMB 10586 that is assembled by a complex trans-AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown. Herein we report the application of NMR spectroscopy, mass spectrometry, chemical probes and in vitro assays to establish the remaining steps of 9HN biosynthesis. These investigations reveal a complex interplay between a novel iterative or "stuttering" KS-AT didomain (MmpF), the multidomain module MmpB and multiple ACPs. This work has important implications for understanding the late-stage biosynthetic steps of mupirocin and will be important for future engineering of related trans-AT biosynthetic pathways (e.g. thiomarinol).