Research Focus:
The overall productivity of any bioprocess is determined by the stability and the efficiency of the biocatalyst, the amount of product produced in a given reaction volume and the yield of product recovery. We use cyanobacteria for splitting water into hydrogen and oxygen driven by energy of the light reaction of photosynthesis. The turnover number of the biocatalyst (kcat in s-1) and its stability over time are determining the amount of hydrogen produced in a given reaction volume (mass of H2 formed per mass of biocatalyst, the total turnover number). This again is limited by the quantum efficiency of the reaction network and thermodynamic and metabolic constraints. Ideally, product recovery is integrated in a continuous production process. We integrate metabolic engineering of natural photosynthesis with continuously operated microreactors based on catalytic biofilms as biocatalysts with membrane technology for maximizing surface to volume ratios and mass transfer rates.
Index:
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2024 (2)
- Bertelmann, C., Mock, M., Schmid, A., Bühler, B. (2024):
Efficiency aspects of regioselective testosterone hydroxylation with highly active CYP450-based whole-cell biocatalysts
Microb. Biotechnol. 17 (1), e14378 10.1111/1751-7915.14378 - Höhmann, S.M., Briol, T.A., Ihle, N., Frick, O., Schmid, A., Bühler, B. (2024):
Glycolate as alternative carbon source for Escherichia coli
J. Biotechnol. 381 , 76 - 85 10.1016/j.jbiotec.2024.01.001
2023 (3)
- Bozan, M., Schmidt, M., Musat, N., Schmid, A., Adrian, L., Bühler, K. (2023):
Spatial organization and proteome of a dual-species cyanobacterial biofilm alter among N2-fixing and non-fixing conditions
mSystems 8 (3), art. 00302-23 10.1128/msystems.00302-23 - Garmasukis, R., Hackl, C., Dusny, C., Elsner, C., Charvat, A., Schmid, A., Abel, B. (2023):
Cryo-printed microfluidics enable rapid prototyping for optical-cell analysis
Microfluid. Nanofluid. 27 , art. 5 10.1007/s10404-022-02613-4 - Toepel, J., Karande, R., Bühler, B., Bühler, K., Schmid, A. (2023):
Photosynthesis driven continuous hydrogen production by diazotrophic cyanobacteria in high cell density capillary photobiofilm reactors
Bioresour. Technol. 373 , art. 128703 10.1016/j.biortech.2023.128703
2022 (6)
- Bertelmann, C., Mock, M., Koch, R., Schmid, A., Bühler, B. (2022):
Hydrophobic outer membrane pores boost testosterone hydroxylation by cytochrome P450 BM3 containing cells
Front. Catal. 2 , art. 887458 10.3389/fctls.2022.887458 - Bozan, M., Schmid, A., Bühler, K. (2022):
Evaluation of self-sustaining cyanobacterial biofilms for technical applications
Biofilm 4 , art. 100073 10.1016/j.bioflm.2022.100073 - Brandenburg, F., Klähn, S., Schmid, A., Krömer, J.O. (2022):
Produktion von Aminosäurederivaten in Cyanobakterien. Production of amino acid derivatives in cyanobacteria
Biospektrum 28 (3), 341 - 343 10.1007/s12268-022-1756-z - Grund, M., Jakob, T., Toepel, J., Schmid, A., Wilhelm, C., Bühler, B. (2022):
Heterologous lactate synthesis in Synechocystis sp. strain PCC 6803 causes a growth condition-dependent carbon sink effect
Appl. Environ. Microb. 88 (8), e00063-22 10.1128/aem.00063-22 - Tüllinghoff, A., Uhl, M.B., Nintzel, F.E.H., Schmid, A., Bühler, B., Toepel, J. (2022):
Maximizing photosynthesis-driven Baeyer-Villiger oxidation efficiency in recombinant Synechocystis sp. PCC6803
Front. Catal. 1 , art. 780474 10.3389/fctls.2021.780474 - Wink, K., van der Loh, M., Hartner, N., Polack, M., Dusny, C., Schmid, A., Belder, D. (2022):
Quantification of biocatalytic transformations by single microbial cells enabled by tailored integration of droplet microfluidics and mass spectrometry
Angew. Chem.-Int. Edit. 61 (29), e202204098 10.1002/anie.202204098
2021 (9)
- Brandenburg, F., Theodosiou, E., Bertelmann, C., Grund, M., Klähn, S., Schmid, A., Krömer, J.O. (2021):
Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803
Metab. Eng. Commun. 12 , e00155 10.1016/j.mec.2020.e00155 - Bühler, K., Bühler, B., Klähn, S., Krömer, J.O., Dusny, C., Schmid, A. (2021):
Biocatalytic production of white hydrogen from water using cyanobacteria
In: Rögner, M. (ed.)
Photosynthesis: Biotechnological applications with microalgae
De Gruyter, Berlin ; Boston, p. 279 - 306 10.1515/9783110716979-011 - Bühler, K., Krömer, J.O., Klähn, S., Bühler, B., Dusny, C., Schmid, A. (2021):
Weißer Wasserstoff made in Leipzig
Biospektrum 27 (3), 335 10.1007/s12268-021-1572-x - Dusny, C., Schmid, A. (2021):
The metabolic flux probe (MFP)—Secreted protein as a non-disruptive information carrier for 13C-based metabolic flux analysis
Int. J. Mol. Sci. 22 (17), art. 9438 10.3390/ijms22179438 - Lai, B., Schneider, H., Tschörtner, J., Schmid, A., Krömer, J.O. (2021):
Technical-scale biophotovoltaics for long-term photo-current generation from Synechocystis sp. PCC6803
Biotechnol. Bioeng. 118 (7), 2637 - 2648 10.1002/bit.27784 - Lai, B., Schneider, H., Tschörtner, J., Schmid, A., Krömer, J.O. (2021):
Inside front cover image, Volume 118, Number 7, July 2021
Biotechnol. Bioeng. 118 (7), ii - ii 10.1002/bit.27411 - Lupacchini, S., Appel, J., Stauder, R., Bolay, P., Klähn, S., Lettau, E., Adrian, L., Lauterbach, L., Bühler, B., Schmid, A., Toepel, J. (2021):
Rewiring cyanobacterial photosynthesis by the implementation of an oxygen-tolerant hydrogenase
Metab. Eng. 68 , 199 - 209 10.1016/j.ymben.2021.10.006 - Salamanca, D., Bühler, K., Engesser, K.-H., Schmid, A., Karande, R. (2021):
Whole-cell biocatalysis using the Acidovorax sp. CHX100 Δ6HX for the production of ω-hydroxycarboxylic acids from cycloalkanes
New Biotech. 60 , 200 - 206 10.1016/j.nbt.2020.10.009 - Welter, E.S., Kött, S., Brandenburg, F., Krömer, J.O., Goepel, M., Schmid, A., Gläser, R. (2021):
Figures of merit for photocatalysis: Comparison of NiO/La-NaTaO3 and Synechocystis sp. PCC 6803 as a semiconductor and a bio-photocatalyst for water splitting
Catalysts 11 (11), art. 1415 10.3390/catal11111415
2020 (3)
- Mock, M., Schmid, A., Bühler, K. (2020):
Directed reaction engineering boosts succinate formation of Synechocystis sp. PCC 6803_Δsll1625
Biotechnol. J. 15 (11), art. 2000127 10.1002/biot.202000127 - Schirmer, M., Wink, K., Ohla, S., Belder, D., Schmid, A., Dusny, C. (2020):
Conversion efficiencies of a few living microbial cells detected at a high throughput by droplet-based ESI-MS
Anal. Chem. 92 (15), 10700 - 10708 10.1021/acs.analchem.0c01839 - Willrodt, C., Gröning, J.A.D., Nerke, P., Koch, R., Scholtissek, A., Heine, T., Schmid, A., Bühler, B., Tischler, D. (2020):
Highly efficient access to (S)-sulfoxides utilizing a promiscuous flavoprotein monooxygenase in a whole-cell biocatalyst format
ChemCatChem 12 (17), 4664 - 4671 10.1002/cctc.201901894
2019 (12)
- David, C., Schmid, A., Bühler, K. (2019):
Cellular physiology controls photoautotrophic production of 1,2‐propanediol from pools of CO2 and glycogen
Biotechnol. Bioeng. 116 (4), 882 - 892 10.1002/bit.26883 - Dusny, C., Lohse, M., Reemtsma, T., Schmid, A., Lechtenfeld, O.J. (2019):
Quantifying a biocatalytic product from a few living microbial cells using microfluidic cultivation coupled to FT-ICR-MS
Anal. Chem. 91 (11), 7012 - 7018 10.1021/acs.analchem.9b00978 - Grund, M., Jakob, T., Wilhelm, C., Bühler, B., Schmid, A. (2019):
Electron balancing under different sink conditions reveals positive effects on photon efficiency and metabolic activity of Synechocystis sp. PCC 6803
Biotechnol. Biofuels 12 , art. 43 10.1186/s13068-019-1378-y - Halan, B., Tschörtner, J., Schmid, A. (2019):
Generating electric current by bioartificial photosynthesis
In: Harnisch, F., Holtmann, D. (eds.)
Bioelectrosynthesis
Adv. Biochem. Eng. Biotechnol. 167
Springer Nature, p. 361 - 393 10.1007/10_2017_44 - Heuschkel, I., Hoschek, A., Schmid, A., Bühler, B., Karande, R., Bühler, K. (2019):
Data on mixed trophies biofilm for continuous cyclohexane oxidation to cyclohexanol using Synechocystis sp. PCC 6803
Data Brief 25 , art. 104059 10.1016/j.dib.2019.104059 - Heuschkel, I., Hoschek, A., Schmid, A., Bühler, B., Karande, R., Bühler, K. (2019):
Mixed-trophies biofilm cultivation in capillary reactors
MethodsX 6 , 1822 - 1831 10.1016/j.mex.2019.07.021 - Hoschek, A., Bühler, B., Schmid, A. (2019):
Stabilization and scale‐up of photosynthesis‐driven ω‐hydroxylation of nonanoic acid methyl ester by two‐liquid phase whole‐cell biocatalysis
Biotechnol. Bioeng. 116 (8), 1887 - 1900 10.1002/bit.27006 - Hoschek, A., Heuschkel, I., Schmid, A., Bühler, B., Karande, R., Bühler, K. (2019):
Mixed-species biofilms for high-cell-density application of Synechocystis sp. PCC 6803 in capillary reactors for continuous cyclohexane oxidation to cyclohexanol
Bioresour. Technol. 282 , 171 - 178 10.1016/j.biortech.2019.02.093 - Hoschek, A., Toepel, J., Hochkeppel, A., Karande, R., Bühler, B., Schmid, A. (2019):
Light‐dependent and aeration‐independent gram‐scale hydroxylation of cyclohexane to cyclohexanol by CYP450 harboring Synechocystis sp. PCC 6803
Biotechnol. J. 14 (8), art. 1800724 10.1002/biot.201800724 - Mock, M., Schmid, A., Bühler, K. (2019):
Photoautotrophic production of succinate via the oxidative branch of the tricarboxylic acid cycle influences glycogen accumulation in Synechocystis sp. PCC 6803
Algal Res. 43 , art. 101645 10.1016/j.algal.2019.101645 - Ütkür, F.Ö., Schmid, A., Bühler, B. (2019):
Anaerobic C-H oxyfunctionalization: Coupling of nitrate reduction and quinoline hydroxylation in recombinant Pseudomonas putida
Biotechnol. J. 14 (8), art. 1800615 10.1002/biot.201800615 - Volmer, J., Lindmeyer, M., Seipp, J., Schmid, A., Bühler, B. (2019):
Constitutively solvent-tolerant Pseudomonas taiwanensis VLB120ΔCΔttgV supports particularly high styrene epoxidation activities when grown under glucose excess conditions
Biotechnol. Bioeng. 116 (5), 1089 - 1101 10.1002/bit.26924
2018 (5)
- David, C., Schmid, A., Adrian, L., Wilde, A., Bühler, K. (2018):
Production of 1,2-propanediol in photoautotrophic Synechocystis is linked to glycogen turn-over
Biotechnol. Bioeng. 115 (2), 300 - 311 10.1002/bit.26468 - Hoschek, A., Schmid, A., Bühler, B. (2018):
In situ O2 generation for biocatalytic oxyfunctionalization reactions
ChemCatChem 10 (23), 5366 - 5371 10.1002/cctc.201801262 - Karande, R., Salamanca, D., Schmid, A., Buehler, K. (2018):
Biocatalytic conversion of cycloalkanes to lactones using an in-vivo cascade in Pseudomonas taiwanensis VLB120
Biotechnol. Bioeng. 115 (2), 312 - 320 10.1002/bit.26469 - Oehling, V., Klaassen, P., Frick, O., Dusny, C., Schmid, A. (2018):
L-Arabinose triggers its own uptake via induction of the arabinose-specific Gal2p transporter in an industrial Saccharomyces cerevisiae strain
Biotechnol. Biofuels 11 , art. 231 10.1186/s13068-018-1231-8 - Schaffer, S., Schmid, A. (2018):
Aminolauric acid: From design of a multistep synthesis route to large‐scale process development
Chem. Ing. Tech. 90 (9), 1334 - 1334 10.1002/cite.201855436
2017 (11)
- Fritzsch, F.S.O., Blank, L.M., Dusny, C., Schmid, A. (2017):
Miniaturized octupole cytometry for cell type independent trapping and analysis
Microfluid. Nanofluid. 21 (8), art. 130 10.1007/s10404-017-1969-5 - Halan, B., Vassilev, I., Lang, K., Schmid, A., Buehler, K. (2017):
Growth of Pseudomonas taiwanensis VLB120ΔC biofilms in the presence of n-butanol
Microb. Biotechnol. 10 (4), 745 - 755 10.1111/1751-7915.12413 - Hoschek, A., Bühler, B., Schmid, A. (2017):
Overcoming the gas-liquid mass transfer of oxygen by coupling photosynthetic water oxidation with biocatalytic oxyfunctionalization
Angew. Chem.-Int. Edit. 56 (47), 15146 - 15149 10.1002/anie.201706886 - Kadisch, M., Julsing, M.K., Schrewe, M., Jehmlich, N., Scheer, B., von Bergen, M., Schmid, A., Bühler, B. (2017):
Maximization of cell viability rather than biocatalyst activity improves whole-cell ω-oxyfunctionalization performance
Biotechnol. Bioeng. 114 (4), 874 - 884 10.1002/bit.26213 - Kadisch, M., Schmid, A., Bühler, B. (2017):
Hydrolase BioH knockout in E. coli enables efficient fatty acid methyl ester bioprocessing
J. Ind. Microbiol. Biotechnol. 44 (3), 339 - 351 10.1007/s10295-016-1890-z - Kadisch, M., Willrodt, C., Hillen, M., Bühler, B., Schmid, A. (2017):
Maximizing the stability of metabolic engineering-derived whole-cell biocatalysts
Biotechnol. J. 12 (8), art. 1600170 10.1002/biot.201600170 - Rosenthal, K., Oehling, V., Dusny, C., Schmid, A. (2017):
Beyond the bulk: disclosing the life of single microbial cells
FEMS Microbiol. Rev. 41 (6), 751 - 780 10.1093/femsre/fux044 - Schmutzler, K., Kupitz, K., Schmid, A., Buehler, K. (2017):
Hyperadherence of Pseudomonas taiwanensis VLB120ΔC increases productivity of (S)-styrene oxide formation
Microb. Biotechnol. 10 (4), 735 - 744 10.1111/1751-7915.12378 - Theodosiou, E., Breisch, M., Julsing, M.K., Falcioni, F., Bühler, B., Schmid, A. (2017):
An artificial TCA cycle selects for efficient α-ketoglutarate dependent hydroxylase catalysis in engineered Escherichia coli
Biotechnol. Bioeng. 114 (7), 1511 - 1520 10.1002/bit.26281 - Volmer, J., Schmid, A., Bühler, B. (2017):
The application of constitutively solvent-tolerant P. taiwanensis VLB120ΔCΔttgV for stereospecific epoxidation of toxic styrene alleviates carrier solvent use
Biotechnol. J. 12 (7), art. 1600558 10.1002/biot.201600558 - Willrodt, C., Halan, B., Karthaus, L., Rehdorf, J., Julsing, M.K., Buehler, K., Schmid, A. (2017):
Continuous multistep synthesis of perillic acid from limonene by catalytic biofilms under segmented flow
Biotechnol. Bioeng. 114 (2), 281 - 290 10.1002/bit.26071
2016 (10)
- Dusny, C., Schmid, A. (2016):
Neue Einblicke in die Welt isolierter Mikroben
Biospektrum 22 (7), 708 - 711 10.1007/s12268-016-0748-2 - Dusny, C., Schmid, A. (2016):
The MOX promoter in Hansenula polymorpha is ultrasensitive to glucose-mediated carbon catabolite repression
FEMS Yeast Res. 16 (6), fow067 10.1093/femsyr/fow067 - Halan, B., Karande, R., Buehler, K., Schmid, A. (2016):
Catalytic Pseudomonas taiwanensis VLB120ΔC biofilms thrive in a continuous pure styrene generated by multiphasic segmented flow in a capillary microreactor
J. Flow Chem. 6 (1), 39 - 42 10.1556/1846.2015.00037 - Karande, R., Debor, L., Salamanca, D., Bogdahn, F., Engesser, K.-H., Buehler, K., Schmid, A. (2016):
Continuous cyclohexane oxidation to cyclohexanol using a novel cytochrome P450 monooxygenase from Acidovorax sp. CHX100 in recombinant P. taiwanensis VLB120 biofilms
Biotechnol. Bioeng. 113 (1), 52 - 61 10.1002/bit.25696 - Karande, R., Schmid, A., Buehler, K. (2016):
Applications of multiphasic microreactors for biocatalytic reactions
Org. Process Res. Dev. 20 (2), 361 - 370 10.1021/acs.oprd.5b00352 - Ladkau, N., Assmann, M., Schrewe, M., Julsing, M.K., Schmid, A., Bühler, B. (2016):
Efficient production of the Nylon 12 monomer ω-aminododecanoic acid methyl ester from renewable dodecanoic acid methyl ester with engineered Escherichia coli
Metab. Eng. 36 , 1 - 9 10.1016/j.ymben.2016.02.011 - Lange, K., Schmid, A., Julsing, M.K. (2016):
Δ9-Tetrahydrocannabinolic acid synthase: The application of a plant secondary metabolite enzyme in biocatalytic chemical synthesis
J. Biotechnol. 233 , 42 - 48 10.1016/j.jbiotec.2016.06.022 - Schmutzler, K., Kracht, O.N., Schmid, A., Buehler, K. (2016):
Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120
Appl. Microbiol. Biotechnol. 100 (1), 347 - 360 10.1007/s00253-015-7006-2 - Sudarsan, S., Blank, L.M., Dietrich, A., Vielhauer, O., Takors, R., Schmid, A., Reuss, M. (2016):
Dynamics of benzoate metabolism in Pseudomonas putida KT2440
Metab. Eng. Commun. 3 , 97 - 110 10.1016/j.meteno.2016.03.005 - Willrodt, C., Hoschek, A., Bühler, B., Schmid, A., Julsing, M.K. (2016):
Decoupling production from growth by magnesium sulfate limitation boosts de novo limonene production
Biotechnol. Bioeng. 113 (6), 1305 - 1314 10.1002/bit.25883
2015 (17)
- Collins, J., Grund, M., Brandenbusch, C., Sadowski, G., Schmid, A., Bühler, B. (2015):
The dynamic influence of cells on the formation of stable emulsions in organic–aqueous biotransformations
J. Ind. Microbiol. Biotechnol. 42 (7), 1011 - 1026 10.1007/s10295-015-1621-x - David, C., Bühler, K., Schmid, A. (2015):
Stabilization of single species Synechocystis biofilms by cultivation under segmented flow
J. Ind. Microbiol. Biotechnol. 42 (7), 1083 - 1089 10.1007/s10295-015-1626-5 - Dusny, C., Grünberger, A., Probst, C., Wiechert, W., Kohlheyer, D., Schmid, A. (2015):
Technical bias of microcultivation environments on single-cell physiology
Lab Chip 15 (8), 1822 - 1834 10.1039/c4lc01270d - Dusny, C., Schmid, A. (2015):
Challenging biological limits with microfluidic single cell analysis
Microb. Biotechnol. 8 (1), 23 - 25 10.1111/1751-7915.12252 - Dusny, C., Schmid, A. (2015):
Microfluidic single-cell analysis links boundary environments and individual microbial phenotypes
Environ. Microbiol. 17 (6), 1839 - 1856 10.1111/1462-2920.12667 - Köhler, K.A.K., Rühl, J., Blank, L.M., Schmid, A. (2015):
Integration of biocatalyst and process engineering for sustainable and efficient n-butanol production
Eng. Life Sci. 15 (1), 4 - 19 10.1002/elsc.201400041 - Lang, K., Buehler, K., Schmid, A. (2015):
Multistep synthesis of (S)-3-hydroxyisobutyric acid from glucose using Pseudomonas taiwanensis VLB120 B83 T7 catalytic biofilms
Adv. Synth. Catal. 357 (8), 1919 - 1927 10.1002/adsc.201500205 - Lange, K., Schmid, A., Julsing, M.K. (2015):
Δ9-Tetrahydrocannabinolic acid synthase production in Pichia pastoris enables chemical synthesis of cannabinoids
J. Biotechnol. 211 , 68 - 76 10.1016/j.jbiotec.2015.06.425 - Lindmeyer, M., Jahn, M., Vorpahl, C., Müller, S., Schmid, A., Bühler, B. (2015):
Variability in subpopulation formation propagates into biocatalytic variability of engineered Pseudomonas putida strains
Front. Microbiol. 6 , art. 1042 10.3389/fmicb.2015.01042 - Lindmeyer, M., Meyer, D., Kuhn, D., Bühler, B., Schmid, A. (2015):
Making variability less variable: matching expression system and host for oxygenase-based biotransformations
J. Ind. Microbiol. Biotechnol. 42 (6), 851 - 866 10.1007/s10295-015-1615-8 - Rosenthal, K., Falke, F., Frick, O., Dusny, C., Schmid, A. (2015):
An inert continuous microreactor for the isolation and analysis of a single microbial cell
Micromachines 6 (12), 1836 - 1855 10.3390/mi6121459 - Salamanca, D., Karande, R., Schmid, A., Dobslaw, D. (2015):
Novel cyclohexane monooxygenase from Acidovorax sp. CHX100
Appl. Microbiol. Biotechnol. 99 (16), 6889 - 6897 10.1007/s00253-015-6599-9 - Schmutzler, K., Schmid, A., Buehler, K. (2015):
A three-step method for analysing bacterial biofilm formation under continuous medium flow
Appl. Microbiol. Biotechnol. 99 (14), 6035 - 6047 10.1007/s00253-015-6628-8 - Theodosiou, E., Frick, O., Bühler, B., Schmid, A. (2015):
Metabolic network capacity of Escherichia coli for Krebs cycle-dependent proline hydroxylation
Microb. Cell. Fact. 14 , art. 108 10.1186/s12934-015-0298-1 - Volmer, J., Schmid, A., Bühler, B. (2015):
Guiding bioprocess design by microbial ecology
Curr. Opin. Microbiol. 25 , 25 - 32 10.1016/j.mib.2015.02.002 - Willrodt, C., Hoschek, A., Bühler, B., Schmid, A., Julsing, M.K. (2015):
Coupling limonene formation and oxyfunctionalization by mixed-culture resting cell fermentation
Biotechnol. Bioeng. 112 (9), 1738 - 1750 10.1002/bit.25592 - Willrodt, C., Karande, R., Schmid, A., Julsing, M.K. (2015):
Guiding efficient microbial synthesis of non-natural chemicals by physicochemical properties of reactants
Curr. Opin. Biotechnol. 35 , 52 - 62 10.1016/j.copbio.2015.03.010