Mixing of oxidized and bilayer phospholipids

Composition and phase dependence of the mixing of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), with the oxidized phospholipid, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) were investigated by characterizing the aggregation states of DPPC/PGPC and DOPC/PGPC using a fluorescence quenching assay, dynamic light scattering, and time-resolved fluorescence quenching in the temperature range 5–60 °C. PGPC forms 3.5 nm radii micelles of aggregation number 33. In the gel phase, DPPC and PGPC fuse to form mixed vesicles for PGPC molar fraction, X_PGPC ≤ 0.3 and coexisting vesicles and micelles at higher X_PGPC. Data suggest that liquid phase DPPC at 50 °C forms mixed vesicles with segregated or hemi fused DPPC and PGPC for X_PGPC ≤ 0.3. At 60 °C, DPPC and PGPC do not mix, but form coexisting vesicles and micelles. DOPC and PGPC do not mix in any proportion in the liquid phase. Two dissimilar aggregates of the sizes of vesicles and PGPC micelles were observed for all X_PGPC for T ≥ 22 °C. DOPC–PGPC and DPPC–PGPC mixing is non-ideal for X_PGPC > 0.3 in both gel and fluid phases resulting in exclusion of PGPC from the bilayer. Formation of mixed vesicles is favored in the gel phase but not in the liquid phase for X_PGPC ≤ 0.3. For X_PGPC ≤ 0.3, aggregation states change progressively from mixed vesicles in the gel phase to component segregated mixed vesicles in the liquid phase close to the chain melting transition temperature to separated coexisting vesicles and micelles at higher temperatures.     

Non-bilayer structures in mitochondrial membranes regulate ATP synthase activity

Cardiolipin (CL) is an anionic phospholipid at the inner mitochondrial membrane (IMM) that facilitates the formation of transient non-bilayer (non-lamellar) structures to maintain mitochondrial integrity. CL modulates mitochondrial functions including ATP synthesis. However, the biophysical mechanisms by which CL generates non-lamellar structures and the extent to which these structures contribute to ATP synthesis remain unknown. We hypothesized that CL and ATP synthase facilitate the formation of non-bilayer structures at the IMM to stimulate ATP synthesis. By using ¹H NMR and ³¹P NMR techniques, we observed that increasing the temperature (8 °C to 37 °C), lowering the pH (3.0), or incubating intact mitochondria with CTII - an IMM-targeted toxin that increases the formation of immobilized non-bilayer structures - elevated the formation of non-bilayer structures to stimulate ATP synthesis. The F₀ sector of the ATP synthase complex can facilitate the formation of non-bilayer structures as incubating model membranes enriched with IMM-specific phospholipids with exogenous DCCD-binding protein of the F₀ sector (DCCD-BPF) elevated the formation of immobilized non-bilayer structures to a similar manner as CTII. Native PAGE assays revealed that CL, but not other anionic phospholipids, specifically binds to DCCD-BPF to promote the formation of stable lipid-protein complexes. Mechanistically, molecular docking studies identified two lipid binding sites for CL in DCCD-BPF. We propose a new model of ATP synthase regulation in which CL mediates the formation of non-bilayer structures that serve to cluster protons and ATP synthase complexes as a mechanism to enhance proton translocation to the F₀ sector, and thereby increase ATP synthesis.     

Thermotropic and structural effects of poly(malic acid) on fully hydrated multilamellar DPPC–water systems

The thermotropic and structural effects of low molecular weight poly(malic acid) (PMLA) on fully hydrated multilamellar dipalmitoylphosphatidylcholine (DPPC)–water systems were investigated using differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), and freeze-fracture transmission electron microscopy (FFTEM). Systems of 20 wt% DPPC concentration and 1 and 5 wt% PMLA to lipid ratios were studied. The PMLA derivatives changed the thermal behavior of DPPC significantly and caused a drastic loss in correlation between lamellae in the three characteristic thermotropic states (i.e., in the gel, rippled gel and liquid crystalline phases). In the presence of PBS or NaCl, the perturbation was more moderate. The structural behavior on the atomic level was revealed by FTIR spectroscopy. The molecular interactions between DPPC and PMLA were simulated via modeling its measured infrared spectra, and their peculiar spectral features were interpreted. Through this interpretation, the poly(malic acid) is inferred to attach to the headgroups of the phospholipids through hydrogen bonds between the free hydroxil groups of PMLA and the phosphodiester groups of DPPC.     

Regulation of plasma membrane Ca2 +-ATPase activity by acetylated tubulin: Influence of the lipid environment

We demonstrated previously that acetylated tubulin inhibits plasma membrane Ca^2 +-ATPase (PMCA) activity in plasma membrane vesicles (PMVs) of rat brain through a reversible interaction. Dissociation of the PMCA/tubulin complex leads to restoration of ATPase activity. We now report that, when the enzyme is reconstituted in phosphatidylcholine vesicles containing acidic or neutral lipids, tubulin not only loses its inhibitory effect but is also capable of activating PMCA. This alteration of the PMCA-inhibitory effect of tubulin was dependent on concentrations of both lipids and tubulin. Tubulin (300 μg/ml) in combination with acidic lipids at concentrations > 10%, increased PMCA activity up to 27-fold. The neutral lipid diacylglycerol (DAG), in combination with 50 μg/ml tubulin, increased PMCA activity > 12-fold, whereas tubulin alone at high concentration (≥ 300 μg/ml) produced only 80% increase. When DAG was generated in situ by phospholipase C incubation of PMVs pre-treated with exogenous tubulin, the inhibitory effect of tubulin on PMCA activity (ATP hydrolysis, and Ca^2 + transport within vesicles) was reversed. These findings indicate that PMCA is activated independently of surrounding lipid composition at low tubulin concentrations (< 50 μg/ml), whereas PMCA is activated mainly by reconstitution in acidic lipids at high tubulin concentrations. Regulation of PMCA activity by tubulin is thus dependent on both membrane lipid composition and tubulin concentration.     

Lipid-mediated regulation of pore-forming activity of syringomycin E by thyroid hormones and xanthene dyes

The effects of dipole modifiers, thyroid hormones (thyroxine and triiodothyronine) and xanthene dyes (Rose Bengal, phloxineB, erythrosin, eosinY and fluorescein) on the pore-forming activity of the lipopeptide syringomycin E (SRE) produced by Pseudomonas syringae were studied in a model bilayer. Thyroxine does not noticeably influence the steady-state number of open SRE channels (N_op), whereas triiodothyronine decreases it 10-fold at − 50 mV. Rose Bengal, phloxine B and erythrosin significantly increase N_op by 350, 100 and 70 times, respectively. Eosin Y and fluorescein do not practically affect the pore-forming activity of SRE. Recently, we showed that hormones decrease the dipole potential of lipid bilayers by approximately 60 mV at 50 μM, while Rose Bengal, phloxine B and erythrosin at 2.5 μM reduce the membrane dipole potential by 120, 80 and 50 mV, respectively. In the present study using differential scanning microcalorimetry, confocal fluorescence microscopy, the calcein release technique and measurements of membrane curvature elasticity, we show that triiodothyronine strongly affects the fluidity of model membranes: its addition leads to a significant decrease in the temperature and cooperativity of the main phase transition of DPPC, calcein leakage from DOPC vesicles, fluidization of solid domains in DOPC/DPPC liposomes, and promotion of lipid curvature stress. Thyroxine exerts a weaker effect. Xanthene dyes do not influence the phase transition of DPPC. Despite the decrease in the dipole potential, thyroid hormones modulate SRE channels predominantly via the elastic properties of the membrane, whereas the xanthene dyes Rose Bengal, phloxine B and erythrosine affect SRE channels via bilayer electrostatics.     

Binding of peptides corresponding to the carboxy-terminal region of human-β-defensins-1–3 with model membranes investigated by isothermal titration calorimetry

Human-β-defensins HBD-1–3 are important components of the innate immune system. Synthetic peptides Phd-1–3 with a single disulphide bond, spanning the cationic C-terminal region of HBD-1–3, have antimicrobial activity. The interaction of Phd-1–3 with model membranes was investigated using isothermal titration calorimetry (ITC) and steady-state fluorescence polarization to understand the biophysical basis for the mechanism of antimicrobial action. Calorimetric titration of POPE:POPG (7:3) vesicles with peptides at 25 °C and 37 °C showed complex profiles with two distinct regions of heat changes. The data indicate binding of Phd-1–3 at 37 °C to both negative and zwitterionic lipid vesicles is exothermic with low enthalpy values (ΔH ~ ? 1.3 to ? 2.8 kcal/mol) as compared to amphipathic helical antibacterial peptides. The adsorption of peptides to negatively charged lipid membranes is modulated by electrostatic interactions that are described by surface partition equilibrium model using Gouy–Chapman theory. However, this model could not explain the isotherms of peptide binding to zwitterionic lipid vesicles. Fluorescence polarization of TMA-DPH (1-[4-(trimethylammonio) phenyl]-6-phenyl-1,3,5-hexatriene) and DPH (1,6-diphenyl-1,3,5-hexatriene) located in the head group and acyl chain region respectively, indicates that the peptides interact with interfacial region of negatively charged membranes. Based on the results obtained, we conclude that adsorption of cationic peptides Phd-1–3 on lipid surface do not result in conformational change or pore formation. It is proposed that interaction of Phd-1–3 with the negatively charged lipid head group causes membrane destabilization, which in turn affects the efficient functioning of cytoplasmic membrane proteins in bacteria, resulting in cell death.     

Partitioning of perfluorooctanoate into phosphatidylcholine bilayers is chain length-independent

The chain length dependence of the interaction of PFOA, a persistent environmental contaminant, with dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) was investigated using steady-state fluorescence anisotropy spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). PFOA caused a linear depression of the main phase transition temperature T_m while increasing the width of the phase transition of all three phosphatidylcholines. Although PFOA's effect on T_m and the transition width decreased in the order DMPC > DPPC > DSPC, its relative effect on the phase behavior was largely independent of the phosphatidylcholine. PFOA caused swelling of DMPC but not DPPC and DSPC liposomes at 37 °C in the DLS experiments, which suggests that PFOA partitions more readily into bilayers in the fluid phase. These findings suggest that PFOA's effect on the phase behavior of phosphatidylcholines depends on the cooperativity and state (i.e., gel versus liquid phase) of the membrane. DLS experiments are also consistent with partial liposome solubilization at PFOA/lipid molar ratios > 1, which suggests the formation of mixed PFOA–lipid micelles.     

Efficient oleaginous yeasts for lipid production from lignocellulosic sugars and effects of lignocellulose degradation compounds on growth and lipid production

Microbial lipid production using lignocellulosic biomass is considered an alternative for biodiesel production. In this study, 418 yeast strains were screened to find efficient oleaginous yeasts which accumulated large quantities of lipid when cultivated in lignocellulosic sugars. Preliminary screening by Nile red staining revealed that 142 strains contained many or large lipid bodies. These strains were selected for quantitative analysis of lipid accumulation by shaking flask cultivation in nitrogen-limited medium II containing 70 g/L glucose or xylose or mixture of glucose and xylose in a ratio of 2:1. Rhodosporidium fluviale DMKU-SP314 produced the highest lipid concentration of 7.9 g/L when cultivated in the mixture of glucose and xylose after 9 days of cultivation, which was 55.0% of dry biomass (14.3 g/L). The main composition of fatty acids were oleic acid (40.2%), palmitic acid (25.2%), linoleic acid (17.9%) and stearic acid (11.1%). Moreover, the strain DMKU-SP314 could grow and produce lipid in a medium containing predominantly lignocellulose degradation products, namely, acetic acid, formic acid, furfural, 5-hydroxymethylfurfural (5-HMF) and vanillin, with however, some inhibitory effects. This strain showed high tolerance to acetic acid, 5-HMF and vanillin. Therefore, R. fluviale DMKU-SP314 is a promising strain for lipid production from lignocellulosic hydrolysate.     

Pentacyclic triterpenes as α-glucosidase and α-amylase inhibitors: Structure-activity relationships and the synergism with acarbose

In this paper, the inhibition of α-amylase and α-glucosidase by nine pentacyclic triterpenes was determined. For α-amylase inhibitory activity, the IC₅₀ values of ursolic acid, corosolic acid, and oleanolic acid were 22.6 ± 2.4 μM, 31.2 ± 3.4 μM, and 94.1 ± 6.7 μM, respectively. For α-glucosidase inhibition, the IC₅₀ values of ursolic acid, corosolic acid, betulinic acid, and oleanolic acid were 12.1 ± 1.0 μM, 17.2 ± 0.9 μM, 14.9 ± 1.9 μM, and 35.6 ± 2.6 μM, respectively. The combination of corosolic acid and oleanolic acid with acarbose showed synergistic inhibition against α-amylase. The combination of the tested triterpenes with acarbose mainly exhibited additive inhibition against α-glucosidase. Kinetic studies revealed that corosolic acid and oleanolic acid showed non-competitive inhibition and acarbose showed mixed-type inhibition against α-amylase. The results provide valuable implications for the triterpenes (ursolic acid, corosolic acid, and oleanolic acid) alone or in combination with acarbose as a therapeutic agent for the treatment of diabetes mellitus.     

Effect of polyethylene glycol,urea and sunflower meal on olive (Olea europaea var. europaea) leaf fermentation in continuous fermentors

A continuous culture system, inoculated with rumen liquor from goats or sheep, was used to study fermentation characteristics of olive leaves (OL). The effects of adding polyethylene glycol (PEG 4000 MW; 0, 2 or 20 g/100 g OL) and/or supplementing with urea (U) or sunflower meal (SM) (1.0 g N/100 g OM) were also studied. Olive leaf fermentation promoted low VFA production (35.2 mmol/d), predominantly of acetic acid, and low efficiency of VFA production (4.91 mol/kg digestible carbohydrates, DCHO). Both values increased with N supplementation, but effects of PEG were variable. No differences ascribed to the rumen inoculum origin were observed. The ammonia N concentration was increased only by supplementation with U. Total and amino acid N output was low and increased with N addition, but it was not affected by PEG treatment. No differences ascribed to the inoculum origin were observed concerning microbial N production rate or efficiency (g N/kg DCHO). There was no clear difference between sources of supplementary N regarding bacterial protein synthesis. On the basis of PEG results, the effect of tannins on OL fermentation was not important.     

Effects of nitrogen concentration and media replacement on cell growth and lipid production of oleaginous marine microalga Nannochloropsis oceanica DUT01

Cell growth and lipid production of a marine microalga Nannochloropsis oceanica DUT01 were investigated, and fresh medium replacement with different ratios to promote long term cell growth and lipid accumulation was also tested. The highest lipid content reached 64% in nitrogen deplete f/2 medium containing 37.5 mg/L NaNO₃ combined with 1/5 fresh medium replacement, however, the highest lipid titer (0.6 g/L) and lipid productivity (31 mg/L/d) were achieved using BG11 medium containing 1.5 g/L NaNO₃, taking advantage of 1/5 fresh medium replacement as well, which corresponded to the maximum biomass production of 1.4 g/L, highlighting the importance of high biomass accumulation for efficient lipid production. When biomass compositions were monitored throughout the culture, decreased protein content was found to be coupled with increased lipid production, whereas relatively stable carbohydrate content was observed. The fatty acids in the lipid of N. oceanica DUT01 comprise over 65% saturated fatty acids and monounsaturated acids (i.e. palmitic acid (C16:0) and oleic acid (C18:1)), suggesting that N. oceanica DUT01 is a promising candidate for biodiesel production. Interestingly, very high content of hexadecadienoic acid (C16:2, about 26–33%) was produced by DUT01, which distinguished this microalga with other microalgae strains reported so far.     

Peripheral arterial stiffness is associated with higher baseline plasma uric acid: A prospective cohort study

This prospective cohort study aimed at identifying association between uric acid (UA) and peripheral arterial stiffness. A prospective cohort longitudinal study was performed according to an average of 4.8 years’ follow-up. The demographic data, anthropometric parameters, peripheral arterial stiffness (carotid-radial pulse-wave velocity, cr-PWV) and biomarker variables including UA were examined at both baseline and follow-up. Pearson’s correlations were used to identify the associations between UA and peripheral arterial stiffness. Further logistic regressions were employed to determine the associations between UA and arterial stiffness. At the end of follow-up, 1447 subjects were included in the analyses. At baseline, cr-PWV (r = 0.200, p < 0.001) was closely associated with UA. Furthermore, the follow-up cr-PWV (r = 0.145, p < 0.001) was also strongly correlated to baseline UA in Pearson’s correlation analysis. Multiple regressions also indicated the association between follow-up cr-PWV (β = 0.493, p = 0.013) and baseline UA level. Logistic regressions revealed that higher baseline UA level was an independent predictor of arterial stiffness severity assessed by cr-PWV at follow-up cross-section. Peripheral arterial stiffness is closely associated with higher baseline UA level. Furthermore, a higher baseline UA level is an independent risk factor and predictor for peripheral arterial stiffness.     

A comparative calorimetric and spectroscopic study of the effects of cholesterol and of the plant sterols β-sitosterol and stigmasterol on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes

We performed comparative DSC and FTIR spectroscopic measurements of the effects of β-sitosterol (Sito) and stigmasterol (Stig) on the thermotropic phase behavior and organization of DPPC bilayers. Sito and Stig are the major sterols in the biological membranes of higher plants, whereas cholesterol (Chol) is the major sterol in mammalian membranes. Sito differs in structure from Chol in having an ethyl group at C24 of the alkyl side-chain, and Stig in having both the C24 ethyl group and trans-double bond at C22. Our DSC studies indicate that the progressive incorporation of Sito and Stig decrease the temperature and cooperativity of the pretransition of DPPC to a slightly lesser and greater extent than Chol, respectively, but the pretransition persists to 10 mol % sterol concentration in all cases. All three sterols produce essentially identical effects on the thermodynamic parameters of the sharp component of the DPPC main phase transition. However, the ability to increase the temperature and decrease the cooperativity and enthalpy of the broad component decreases in the order Chol > Sito > Stig. Nevertheless, at higher Sito/Stig concentrations, there is no evidence of sterol crystallites. Our FTIR spectroscopic studies demonstrate that Sito and especially Stig incorporation produces a smaller ordering of the hydrocarbon chains of fluid DPPC bilayers than does Chol. In general, the presence of a C24 ethyl group in the alkyl side-chain reduces the characteristic effects of Chol on the thermotropic phase behavior and organization of DPPC bilayer membranes, and a trans-double bond at C22 magnifies this effect.     

Effects of culture redox potential on succinic acid production by Corynebacterium crenatum under anaerobic conditions

During mixed-acid fermentation by Corynebacterium crenatum under anaerobic conditions, two moles of NADH are required to synthesize 1 mol of succinic acid. In this work, four controlled culture redox potentials and different carbon sources with different oxidation states were used to investigate the possibility of enhancing the succinic acid production by increasing the availability of NADH. When the culture redox potential was ?300 mV, the yield of succinic acid was 0.31 g/g, representing a 72% increase compared with the yield when the culture redox potential was ?40 mV. Meanwhile, the molar ratio of succinic acid/lactic acid increased from 0.27 to 0.48. When 0.1% neutral red was added to the acid production medium, the yield of succinic acid was 0.25 g/g, and the molar ratio of succinic acid/lactic acid was 0.38. Both values were higher than those obtained from glucose only (0.19 g/g, 0.26) or gluconate (0.05 g/g, 0.18). A higher NADH/NAD⁺ ratio and increased enzymatic activity could be achieved to enhance the succinic acid production by manipulating the culture to a more reductive environment.     

Reversible lysozyme immobilization onto N,N′-bis-(3-(4-morpholino)-propyl)-3,4,9,10-perylenetetracarboxylic acid dimide (MPPDI) attached polymeric nanospheres

Novel hydrophobic nanospheres with an average size of 200 nm utilizing N,N′-bis-(3-(4-morpholino)-propyl)-3,4,9,10-perylenetetracarboxylic acid dimide (MPPDI) as a monomer were prepared by surfactant free emulsion polymerization of 2-hydroxyethyl methacrylate (HEMA) and MPPDI conducted in an aqueous dispersion medium. The nanospheres were used for the adsorption of lysozyme. The system parameters, such as effect of the adsorption conditions (i.e. enzyme concentration, medium pH, and temperature) and the reusability of the support were studied. Specific surface area of the nonporous nanospheres was found 664 m²/g. Poly(HEMA–MPPDI) nanospheres were characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis and scanning electron microscopy (SEM). Then, poly(HEMA–MPPDI) nanospheres were used in the adsorption of lysozyme in batch system. Using an optimized adsorption protocol, 400 mg lysozyme/g nanosphere loading capacity was obtained. The adsorption phenomena appeared to follow a typical Langmuir isotherm. Lysozyme could be repeatedly adsorbed and desorbed with poly(HEMA–MPPDI) nanospheres without noticeable loss in the adsorption capacity.     

Determination of asiatic acid in beagle dog plasma after oral administration of Centella asiatica extract by precolumn derivatization RP-HPLC

A novel precolumn derivatization reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV–vis detection for the quantitative determination of total concentration of asiatic acid (AA) in beagle dog plasma is described. AA was extracted with n-hexane-dichloromethane-2-propanol (20:10:1, v/v/v) from plasma, which had been hydrolyzed by acid and derivatized with p-Toluidine. Chromatographic separation was achieved on a C₁₈ column using gradient elution in a water–methanol system. Detection was set at UV wavelength of 248 nm. A calibration curve ranging from 0.01 to 1.5 μg/mL was shown to be linear, and the lower limit of quantification (LLOQ) was 0.01 μg/mL. The intra- and inter-day precisions which were determined by three different concentrations (0.05, 0.2 and 0.8 μg/mL) ranged from 4.4% to 13.1% and 4.6% to 14.2%, respectively. Mean extraction recoveries were no less than 65% for AA and ursolic acid (IS). Plasma samples containing asiatic acid were stable for 30 days at ?20 °C. The method was successfully applied to a pharmacokinetic study in beagle dogs after oral administration of Centella asiatica extract, and the main pharmacokinetic parameters obtained were: T_1/2, 4.29 h; T_max, 2.70 h; C_max, 0.74 μg/mL; AUC_0–t and AUC_0–∞, 3.74 and 3.82 μg h/mL, respectively.     

Surface behavior of peptides from E1 GBV-C protein: Interaction with anionic model membranes and importance in HIV-1 FP inhibition

The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural analogs (E1P8-12), (E1P8-13), and (E1P8-21) with anionic lipid membranes (POPG vesicles and POPG, DPPG or DPPC/DPPG (2:1) monolayers) and their association with HIV-1 fusion peptide (HIV-1 FP) inhibition at the membrane level were studied using biophysical methods. All peptides showed surface activity but leakage experiments in vesicles as well as insertion kinetics in monolayers and lipid/peptide miscibility indicated a low level of interaction: neither E1P8 nor its analogs induced the release of vesicular content and the exclusion pressure values (π_e) were clearly lower than the biological membrane pressure (24–30 mN m^− 1) and the HIV-1 FP (35 mN m^− 1). Miscibility was elucidated in terms of the additivity rule and excess free energy of mixing (G^E). E1P8, E1P8-12 and E1P8-21 (but not E1P8-13) induced expansion of the POPG monolayer. The mixing process is not thermodynamically favored as the positive G^E values indicate. To determine how E1 peptides interfere in the action of HIV-1 FP at the membrane level, mixed monolayers of HIV-1 FP/E1 peptides (2:1) and POPG were obtained. E1P8 and its derivative E1P8-21 showed the greatest HIV-1 FP inhibition. The LC-LE phase lipid behavior was morphologically examined via fluorescence microscopy (FM) and atomic force microscopy (AFM). Images revealed that the E1 peptides modify HIV-1 FP–lipid interaction. This fact may be attributed to a peptide/peptide interaction as indicated by AFM results. Finally, hemolysis assay demonstrated that E1 peptides inhibit HIV-1 FP activity.     

Co-fermentation of lignocellulose-based glucose and inhibitory compounds for lipid synthesis by Rhodococcus jostii RHA1

The recalcitrant nature of lignocellulosic biomass entails pretreatment during which multiple byproducts (e.g., weak acids, furan derivatives, lignin-derived compounds) are generated. Such byproducts are generally inhibitory to fuel-producing microorganisms. In this study, lignin-derived monomers and acetate were co-fermented with glucose by Rhodococcus jostii RHA1 for lipid synthesis. The ability of R. jostii RHA1 to utilize acetate and representative lignin-derived monomers, namely p-coumaric acid, ferulic acid, 4-hydroxylic acid, and vanillic acid, were tested. The experimental results showed that R. jostii RHA1 utilized individual lignin monomers in varying degrees. The mixtures of inhibitory compounds at different levels showed higher toxicity than individual compounds, indicating synergistic effects of these monomers. When the mixture contained lower levels of glucose (5 g/L or below), adaptive-evolved (AE) R. jostii RHA1 utilized such inhibitory mixtures better for lipid synthesis. When the glucose levels were increased to 20 g/L or above, adaption evolution appeared to shorten the lag phase of co-fermentation but not necessarily enhance lipid production. This study demonstrated that R. jostii RHA1 was capable of utilizing commonly unfavorable carbon sources for lipid synthesis, which would also serve as a means to in situ detoxify inhibitory compounds.