Production of indigo by recombinant bacteria

Abstract

Indigo is an economically important dye, especially for the textile industry and the dyeing of denim fabrics for jeans and garments. Around 80,000 tonnes of indigo are chemically produced each year with the use of non-renewable petrochemicals and the use and generation of toxic compounds. As many microorganisms and their enzymes are able to synthesise indigo after the expression of specific oxygenases and hydroxylases, microbial fermentation could offer a more sustainable and environmentally friendly manufacturing platform. Although multiple small-scale studies have been performed, several existing research gaps still hinder the effective translation of these biochemical approaches. No article has evaluated the feasibility and relevance of the current understanding and development of indigo biocatalysis for real-life industrial applications. There is no record of either established or practically tested large-scale bioprocess for the biosynthesis of indigo. To address this, upstream and downstream processing considerations were carried out for indigo biosynthesis. 5 classes of potential biocatalysts were identified, and 2 possible bioprocess flowsheets were designed that facilitate generating either a pre-reduced dye solution or a dry powder product. Furthermore, considering the publicly available data on the development of relevant technology and common bioprocess facilities, possible platform and process values were estimated, including titre, DSP yield, potential plant capacities, fermenter size and batch schedule. This allowed us to project the realistic annual output of a potential indigo biosynthesis platform as 540 tonnes. This was interpreted as an industrially relevant quantity, sufficient to provide an annual dye supply to a single industrial-size denim dyeing plant. The conducted sensitivity analysis showed that this anticipated output is most sensitive to changes in the reaction titer, which can bring a 27.8% increase or a 94.4% drop. Thus, although such a biological platform would require careful consideration, fine-tuning and optimization before real-life implementation, the recombinant indigo biosynthesis was found as already attractive for business exploitation for both, luxury segment customers and mass-producers of denim garments.

Keywords

Bioprocess / Biocatalysis / Commercialization / Heterologous DNA expression / Recombinant biology / Scale up / Sustainability / Vat dye

References

[1] Abduh MY, van Ulden W, Kalpoe V, van de Bovenkamp HH, Manurung R, Heeres HJ. Biodiesel synthesis from Jatropha curcas L. oil and ethanol in a continuous centrifugal contactor separator. Eur J Lipid Sci Technol, 2013, 115: 123-131.

[2] Agerkvist I, Enfors SO. Characterization of E. coli cell disintegrates from a bead mill and high pressure homogenizers. Biotechnol Bioeng, 1990, 36: 1083-1089.

[3] Ajioka J, Yarkoni ORR (2017) Investigating the adoption of a new way of dyeing fabric in India [Online]. https://iteamsonline.org/investigating-the-adoption-of-a-new-way-of-dyeing-fabric-in-india/. Accessed 03 Nov 2022.

[4] Alexandri M, Vlysidis A, Papapostolou H, Tverezovskaya O, Tverezovskiy V, Kookos IK, Koutinas A. Downstream separation and purification of succinic acid from fermentation broths using spent sulphite liquor as feedstock. Sep Purif Technol, 2019, 209: 666-675.

[5] Ameria SP, Jung HS, Kim HS, Han SS, Kim HS, Lee JH. Characterization of a flavin-containing monooxygenase from Corynebacterium glutamicum and its application to production of indigo and indirubin. Biotechnol Lett, 2015, 37: 1637-1644.

[6] Anastassiadis S, Morgunov IG, Kamzolova SV, Finogenova TV. Citric acid production patent review. Recent Pat Biotechnol, 2008, 2: 107-123.

[7] Angelis A, Michailidis D, Antoniadi L, Stathopoulos P, Tsantila V, Nuzillard J-M, Renault J-H, Skaltsounis LA. Pilot continuous centrifugal liquid-liquid extraction of extra virgin olive oil biophenols and gram-scale recovery of pure oleocanthal, oleacein, MFOA, MFLA and hydroxytyrosol. Sep Purif Technol, 2021, 255.

[8] Antony FM, Pal D, Wasewar K. Separation of bio-products by liquid–liquid extraction, 2021, Berlin: De Gruyter.

[9] ARCHROMA (2022) Archroma and Stony Creek Colors to enter strategic partnership to produce Indigold™ high-performance plant-based pre-reduced indigo at scale [Online]. https://www.archroma.com/press/releases/archroma-and-stony-creek-colors-to-enter-strategic-partnership-to-produce-indigold-high-performance-plant-based-pre-reduced-indigo-at-scale. Accessed 05 Nov 2022.

[10] Avantor (2022) Products [Online]. https://us.vwr.com/store/catalog/vwr_products.jsp. Accessed 03 Jul 2022.

[11] Baeyer A, Drewsen V (1882) Darstellung von Indigblau aus Orthonitrobenzaldehyd. Berichte der deutschenchemischen Gesellschaft 15:2856-2864

[12] Bailey JE, Sburlati A, Hatzimanikatis V, Lee K, Renner WA, Tsai PS. Inverse metabolic engineering: a strategy for directed genetic engineering of useful phenotypes. Biotechnol Bioeng, 1996, 52: 109-121.

[13] Balasundaram B, Nesbeth D, Ward JM, Keshavarz-Moore E, Bracewell DG. Step change in the efficiency of centrifugation through cell engineering: co-expression of Staphylococcal nuclease to reduce the viscosity of the bioprocess feedstock. Biotechnol Bioeng, 2009, 104: 134-142.

[14] Balfour-Paul J (2011) Indigo: From mummies to Blue Jeans. London: British Museum

[15] Banoglu E, Jha GG, King RS. Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. Eur J Drug Metab Pharmacokinet, 2001, 26: 235-240.

[16] Barrios DA, D'Antonio J, McCombs NL, Zhao J, Franzen S, Schmidt AC, Sombers LA, Ghiladi RA. Peroxygenase and oxidase activities of dehaloperoxidase-hemoglobin from Amphitrite ornata. J Am Chem Soc, 2014, 136: 7914-7925.

[17] Berger S, Sicker D. Classics in spectroscopy: isolation and structure elucidation of natural products, 2009, New York: John Wiley & Sons.

[18] Berry A, Dodge TC, Pepsin M, Weyler W. Application of metabolic engineering to improve both the production and use of biotech indigo. J Ind Microbiol Biotechnol, 2002, 28: 127-133.

[19] Bhave RR. Cross-flow filtration. Fermentation and biochemical engineering handbook, 1996, Amsterdam: Elsevier.

[20] Bhushan B, Samanta SK, Jain RK. Indigo production by naphthalene-degrading bacteria. Lett Appl Microbiol, 2000, 31: 5-9.

[21] Blackburn RS, Bechtold T, John P. The development of indigo reduction methods and pre-reduced indigo products. Color Technol, 2009, 125: 193-207.

[22] Blaser H, Siegrist U, Steiner H, Studer M, Sheldon R, VAN BEKKUM H. Fine chemicals through heterogeneous catalysis: aromatic nitro compounds, 2001, New York: Wiley.

[23] BLUECONNECTION 2019. The presence and future of indigo and the denim industry

[24] Bracewell DG, Smales CM. The challenges of product- and process-related impurities to an evolving biopharmaceutical industry. Bioanalysis, 2013, 5: 123-126.

[25] Budzianowski WM. High-value low-volume bioproducts coupled to bioenergies with potential to enhance business development of sustainable biorefineries. Renew Sustain Energy Rev, 2017, 70: 793-804.

[26] Cacciuttolo MA, Arunakumari A. Scale-up considerations for biotechnology-derived products. Pharmaceutical process scale-up, 2005, Boca Raton: CRC Press.

[27] Cairo G (2015) Optimization of indirubin and indigo production in E.coli. Honors Theses. Southern Illinois University Carbondale

[28] Carpio M. Current challenges with cell culture scale-up for biologics production. BioPharm Int, 2020, 33: 23-27.

[29] CATUCCI G, TURELLA S, CHEROPKINA H, DE ANGELIS M, GILARDI G, SADEGHI SJ (2022) Green production of indigo and indirubin by an engineered Baeyer–Villiger monooxygenase. Biocatalysis and Agricultural Biotechnology, 44:102458

[30] Centre for Global Equity (2021) Investigating the adoption of a new way of dyeing fabric in India [Online]. https://centreforglobalequality.org/investigating-adoption-new-way-dyeing-fabric-india/. Accessed 01 Apr 2021.

[31] Chakraborty J. Fundamentals and practices in colouration of textiles, 2015, Boca Raton: CRC Press

[32] Charov K, Burkart MD. Quantifying protein-protein interactions of the acyl carrier protein with solvatochromic probes. Methods Enzymol, 2020, 638: 321-340.

[33] CHIT, A., CHIT, A., PAPADIMITROPOULOS, M., KRAHN, M., PARKER, J. & GROOTENDORST, P. 2015. The Opportunity Cost of Capital. INQUIRY: The Journal of Health Care Organization, Provision, and Financing, 52, 004695801558464.

[34] Choi KY. A review of recent progress in the synthesis of bio-indigoids and their biologically assisted end-use applications. Dyes Pigm, 2020, 181.

[35] Christie R. Colour chemistry, 2014, London: Royal society of chemistry

[36] Clark RJH, Cooksey CJ, Daniels MAM, Withnall R. Indigo, woad, and Tyrian Purple: important vat dyes from antiquity to the present. Endeavour (new Series), 1993, 17: 191-199.

[37] Coats (2021) Denim Jeans [Online]. https://coats.com/en/Industries/Apparel/Applications/Denim-jeans. Accessed 22 Jan 2022.

[38] Connor O, Dobson ADW, Hartmans S. Indigo formation by microorganisms expressing styrene monooxygenase activity. Appl Environ Microbiol, 1997, 63: 4287-4291.

[39] Cordin M, Bechtold T, Pham T. Quantification of aniline and N-methylaniline in indigo. Sci Rep, 2021, 11: 21135.

[40] Cossar D. Bioprocessing techniques. Comprehensive biotechnology, 2019, 3, Waterloo: Elsevier, 679-690.

[41] Cotton (2004) Technical Bulletin. Denim fabric manufacturing [Online]. https://www.cottoninc.com/wp-content/uploads/2017/12/ISP-1010-Denim-Fabric-Manufacturing.pdf. Accessed 16 Nov 2021.

[42] Cottonworks (2021) Denim manufacturing: yarn processes [Online]. https://www.cottonworks.com/en/topics/sourcing-manufacturing/denim/yarn-processes/. Accessed 16 Nov 2022.

[43] Craik JD, Khan D, Afifi R. The safety of intravenous indigo carmine to assess ureteric patency during transvaginal uterosacral suspension of the vaginal vault. J Pelvic Med Surg, 2009, 15: 11-15.

[44] Crater JS, Lievense JC. Scale-up of industrial microbial processes. FEMS Microbiol Lett, 2018

[45] Crocker L, Fruk L. Flavin conjugated polydopamine nanoparticles displaying light-driven monooxygenase activity. Front Chem, 2019, 7: 278.

[46] Cubley (2019) How much yarn do I need for knitted sweaters or cardigans? [Online]. https://www.interweave.com/article/knitting/how-much-yarn-do-i-need/. Accessed 17 May 2022.

[47] Dai C, Ma Q, Li Y, Zhou D, Yang B, Qu Y. Application of an efficient indole oxygenase system from Cupriavidus sp. SHE for indigo production. Bioprocess Biosyst Eng, 2019, 42: 1963-1971.

[48] de Gonzalo G, Ottolina G, Zambianchi F, Fraaije MW, Carrea G. Biocatalytic properties of Baeyer-Villiger monooxygenases in aqueous–organic media. J Mol Catal B Enzym, 2006, 39: 91-97.

[49] de Sá Alves FR, Barreiro EJ, Fraga CA. From nature to drug discovery: the indole scaffold as a 'privileged structure'. Mini Rev Med Chem, 2009, 9: 782-793.

[50] Deeley MC, Yanofsky C. Nucleotide sequence of the structural gene for tryptophanase of Escherichia coli K-12. J Bacteriol, 1981, 147: 787-796.

[51] Dehns (2018) Patenting of medical and biotech inventions [Online]. https://www.dehns.com/cms/document/patenting_of_medical_and_biotech_inventions.pdf. Accessed 17 Jan 2021.

[52] Deloitte (2021) Sustainable manufacturing. From vision to action. [Online]. Available: https://www2.deloitte.com/content/dam/Deloitte/ch/Documents/manufacturing/deloitte-ch-en-sustainable-manufacturing-2021.pdf. Accessed 20 Dec 21.

[53] Denimhunters. 2021. Denim weight: What is an ‘ounce’ and why it matters [Online]. Available: https://denimhunters.com/denim-wiki/denim-explained/denim-weight/. Accessed 16 Dec 2021.

[54] Dhillon GS, Brar SK, Kaur S, Verma M. Bioproduction and extraction optimization of citric acid from Aspergillus niger by rotating drum type solid-state bioreactor. Ind Crops Prod, 2013, 41: 78-84.

[55] Doran PM (1995) Bioprocess engineering principles, Elsevier. https://doi.org/10.1016/B978-012220855-3/50013-4

[56] Dornfeld DA. Moving towards green and sustainable manufacturing. Int J Precis Eng Manuf Green TeChnol, 2014, 1: 63-66.

[57] Doukyu N, Nakano T, Okuyama Y, Aono R. Isolation of an Acinetobacter sp. ST-550 which produces a high level of indigo in a water-organic solvent two-phase system containing high levels of indole. Appl Microbiol Biotechnol, 2002, 58: 543-546.

[58] Doukyu N, Toyoda K, Aono R. Indigo production by Escherichia coli carrying the phenol hydroxylase gene from Acinetobacter sp strain ST-550 in a water-organic solvent two-phase system. Appl Microbiol Biotechnol, 2003, 60: 720-725.

[59] Dutkiewicz T, Piotrowski J. Experimental investigations on the quantitative estimation of aniline absorption in man. Pure Appl Chem, 1961, 3: 319-324.

[60] Dystar (2009) Safety data sheet in accordance with EU Directives. DyStar Indigo Vat 40% solution TACO. [Online]. https://pdf4pro.com/amp/view/safety-data-sheet-transtank-hk-4c0e3e.html. Accessed 05 Aug 2021.

[61] Dystar (2021a) DyStar Indigo Vat 40% Solution [Online]. https://www.dystar.com/products/dyes/featured-dyes/dystar-indigo-vat-40-solution/. Accessed 12 Apr 2021a.

[62] Dystar (2021b) DyStar History [Online]. https://www.dystar.com/history/. Accessed 23 May 2021b.

[63] Echa (2021). Substance Infocard. Aniline [Online]. https://echa.europa.eu/pl/substance-information/-/substanceinfo/100.000.491. Accessed 13 Apr 2021.

[64] Eggeling L, Bott M. A giant market and a powerful metabolism: L-lysine provided by Corynebacterium glutamicum. Appl Microbiol Biotechnol, 2015, 99: 3387-3394.

[65] Ensley BD, Ratzkin BJ, Osslund TD, Simon MJ, Wackett LP, Gibson DT. Expression of naphthalene oxidation genes in Escherichia coli results in the biosynthesis of indigo. Science, 1983, 222: 167-169.

[66] EPA US (1985) Health and Environmental Effects Profile for Aniline. Environmental Criteria and Assessment Office. National Technical Reports Library. Available: https://cfpub.epa.gov/ncea/risk/hhra/recordisplay.cfm?deid=49477. Accessed: 05 Aug 2021.

[67] EPA US (2000) Aniline. Hazard Summary. Available:https://www.epa.gov/sites/default/files/2016-08/documents/aniline.pdf. Accessed: 05 Aug 2021.

[68] ETAD (2022) About us [Online]. https://etad.com/who-we-are/jfm-anchor-about-us. Accessed 05 Nov 2022.

[69] Fabara AN, Fraaije MW. An overview of microbial indigo-forming enzymes. Appl Microbiol Biotechnol, 2020, 104: 925-933.

[70] Farid SS. Process economics of industrial monoclonal antibody manufacture. J Chromatogr B Analyt Technol Biomed Life Sci, 2007, 848: 8-18.

[71] Farid SS, Washbrook J, Titchener-Hooker NJ. Decision-Support Tool for Assessing Biomanufacturing Strategies under Uncertainty: Stainless Steel versus Disposable Equipment for Clinical Trial Material Preparation. Biotechnol Prog, 2008, 21: 486-497.

[72] Fernando Y, Xin WW, Gani ABD. Five Drivers of Eco-Innovation: Insights from Parsimonious Model Using a Content Analysis Approach. International Journal of Disease Control and Containment for Sustainability (IJDCCS), 2016, 1: 12-31.

[73] Fiorentini F, Hatzl AM, Schmidt S, Savino S, Glieder A, Mattevi A. The Extreme Structural Plasticity in the CYP153 Subfamily of P450s Directs Development of Designer Hydroxylases. Biochemistry, 2018, 57: 6701-6714.

[74] First Practice Management (2022) Waste Management/Waste Handling. Hazardous Waste regulations 2005 [Online]. https://www.firstpracticemanagement.co.uk/knowledge-base/general-administration/waste-management-waste-handling/hazardous-waste-regulations/. Accessed 08 Aug 2022.

[75] Fraaije MW, Wu J, Heuts DP, van Hellemond EW, Spelberg JH, Janssen DB. Discovery of a thermostable Baeyer-Villiger monooxygenase by genome mining. Appl Microbiol Biotechnol, 2005, 66: 393-400.

[76] Frabel S, Wagner B, Krischke M, Schmidts V, Thiele CM, Staniek A, Warzecha H. Engineering of new-to-nature halogenated indigo precursors in plants. Metab Eng, 2018, 46: 20-27.

[77] FT Research Team (2018) AMA Herbal brought sustainable Bio Indigo® dye with ‘Life Cycle Analysis’ for denim manufacturers [Online]. https://www.textiletoday.com.bd/ama-herbal-brought-sustainable-bio-indigo-dye-life-cycle-analysis-denim-manufacturers/. Accessed 24 May 2021.

[78] Futures F (2021). Project Coelicolor [Online]. https://faberfutures.com/projects/project-coelicolor/. Accessed 31 Mar 2021.

[79] Garcia-Ochoa F, Gomez E. Bioreactor scale-up and oxygen transfer rate in microbial processes: an overview. Biotechnol Adv, 2009, 27: 153-176.

[80] Garfield S. Mauve: how one man invented a color that changed the world, 2002, New York: WW Norton & Company.

[81] Gelder EA, Jackson SD, Lok CM (2005) The hydrogenation of nitrobenzene to aniline: a new mechanism. Chem Commun (Camb) 28;(4):522–524. https://doi.org/10.1039/b411603h

[82] Gilbert KG, Maule HG, Rudolph B, Lewis M, Vandenburg H, Sales E, Tozzi S, Cooke DT. Quantitative analysis of indigo and indigo precursors in leaves of Isatis spp. and Polygonum tinctorium. Biotechnol Prog, 2004, 20: 1289-1292.

[83] Gillam EMJ, Guengerich FP. Exploiting the versatility of human cytochrome p450 enzymes: the promise of blue roses from biotechnology. IUBMB Life, 2001, 52: 271-277.

[84] Głowacki ED, Voss G, Leonat L, Irimia-Vladu M, Bauer S, Sariciftci NS. Indigo and Tyrian purple—from ancient natural dyes to modern organic semiconductors. Isr J Chem, 2012, 52: 540-551.

[85] González MI, Álvarez S, Riera F, Álvarez R. Economic evaluation of an integrated process for lactic acid production from ultrafiltered whey. J Food Eng, 2007, 80: 553-561.

[86] Gorman D (2020) Why consumers want sustainable products more than ever. Global Web Index (GWI) [Online]. https://blog.globalwebindex.com/chart-of-the-week/sustainable-fashion/. Accessed 01 Apr 2021.

[87] Gregorio NE, Levine MZ, Oza JP. A user’s guide to cell-free protein synthesis. Methods Protocols, 2019, 2: 24.

[88] Groeneveld M, van Beek HL, Duetz WA, Fraaije MW. Identification of a novel oxygenase capable of regiospecific hydroxylation of d-limonene into (+)-trans-carveol. Tetrahedron, 2016, 72: 7263-7267.

[89] HAGEL L, JAGSCHIES G, SOFER G (2008) 4 - Separation Technologies. In: HAGEL L, JAGSCHIES G, SOFER G (eds.) Handbook of Process Chromatography (Second Edition). Amsterdam: Academic Press

[90] Hannemann F, Bichet A, Ewen KM, Bernhardt R. Cytochrome P450 systems—biological variations of electron transport chains. Biochem Biophys Acta, 2007, 1770: 330-344.

[91] Hamamah ZA, Grützner T. Liquid-liquid centrifugal extractors: types and recent applications—a review. ChemBioEng Reviews, 2022, 9: 286-318.

[92] Han GH, Shin H-J, Kim SW. Optimization of bio-indigo production by recombinant E. coli harboring fmo gene. Enzyme Microb Technol, 2008, 42: 617-623.

[93] Han GH, Bang SE, Babu BK, Chang M, Shin H-J, Kim SW. Bio-indigo production in two different fermentation systems using recombinant Escherichia coli cells harboring a flavin-containing monooxygenase gene (fmo). Process Biochem, 2011, 1991(46): 788-791.

[94] HARRISON R, TODD P, RUDGE S, PETRIDES D (2015) Bioseparations Science and Engineering. 2nd edn. Oxford University Press, New York. https://doi.org/10.1093/oso/9780195391817.001.0001

[95] Hazardous Waste Regulations (2005) The Hazardous Waste (England and Wales) Regulations (S.I.2005/895) [Online]. https://www.legislation.gov.uk/uksi/2005/894/note/made.

[96] HSU T M, WELNER D H, RUSS ZN, CERVANTES B, PRATHURI RL, ADAMS PD, DUEBER JE(2018) Employing a biochemical protecting group for a sustainable indigo dyeing strategy. Nat Chem Biol 14:256-261

[97] Humbird D (2015) Aerobic bioreactor scale-up: Modeling and economics [Conference Presentation]. OPTIMIZETM 2015, Boston, United States

[98] Humbird D. Scale-up economics for cultured meat. Biotechnol Bioeng, 2021, 118: 3239-3250.

[99] Humbird D, Davis R, McMillan JD. Aeration costs in stirred-tank and bubble column bioreactors. Biochem Eng J, 2017, 127: 161-166.

[100] HUUE (2021). Huue’s Commercial Website [Online]. Available: https://www.huue.bio/. Accessed 24 May 2021.

[101] INOUE S, MORIYA T, MORITA R, KUWATA K, THUL ST, SARANGI BK, MINAMI Y (2017) Characterization of UDP-glucosyltransferase from Indigofera tinctoria. Plant Physiol Biochem 121:226–233

[102] ISO (2022) Standards by ISO/TC 256. Pigments, dyestuffs and extenders [Online]. https://www.iso.org/committee/618129/x/catalogue/. Accessed 05 Nov 2022.

[103] Jasper W, Günay M. Measurement and control of dyeing. Modelling, simulation and control of the dyeing process, 2014, Amsterdam: Elsevier.

[104] Jin Z, Hu K, Yang F, Nawaz M, Wei H, Jiang Y, Xiao Y, Li J, Hu J, Gao MT. Integrated process for the production of indigo and indirubin in an anaerobic environment at laboratory and pilot level. J Clean Prod, 2022

[105] Kafferlein HU, Broding HC, Bunger J, Jettkant B, Koslitz S, Lehnert M, Marek EM, Blaszkewicz M, Monse C, Weiss T, Bruning T. Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits. Arch Toxicol, 2014, 88: 1419-1426.

[106] Kalum LL, Henrik H, Martin UR. (2014) Enzymatic preparation of indigo dyes and intermediates.

[107] Karamerou EE, Parsons S, Mcmanus MC, Chuck CJ. Using techno-economic modelling to determine the minimum cost possible for a microbial palm oil substitute. Biotechnol Biofuels, 2021

[108] Karana E, Barati B, Giaccardi E. Living artefacts: Conceptualizing livingness as a material quality in everyday artefacts. Int J Des, 2020, 14: 37.

[109] Kawasaki Y (2015) Scalable bio-production of high value products in bacteria. ProQuest Dissertations Publishing.

[110] Keegan G (2021) Indigo Vat Basics [Online]. https://www.grahamkeegan.com/indigo-vat-basics. Accessed 12 Apr 2021.

[111] Kelley B (2009) Industrialization of mAb production technology: The bioprocessing industry at a crossroads. mAbs, 1, 443–452.

[112] Kelly WJ, Muske KR. Optimal operation of high-pressure homogenization for intracellular product recovery. Bioprocess Biosyst Eng, 2004, 27: 25-37.

[113] Khan S, Ullah MW, Siddique R, Nabi G, Manan S, Yousaf M, Hou H. Role of Recombinant DNA Technology to Improve Life. International Journal of Genomics, 2016, 2016: 1-14.

[114] Kim J, Lee P-G, Jung E-O, Kim B-G. In vitro characterization of CYP102G4 from Streptomyces cattleya: A self-sufficient P450 naturally producing indigo. Biochimica et biophysica acta. Proteins and Proteomics, 2018, 1866: 60-67.

[115] Kohlhaupt R, Bergmann UDO. 1993. Purification of indigo. Germany patent application.

[116] Kohlhaupt R, Gaeng M, Haas L, Engelhardt G, Bieg W, Fankhaenel, Matthias 1991. Purification of indigo. US07/684,873.

[117] Korinth G, Schaller KH, Bader M, Bartsch R, Göen T, Rossbach B, Drexler H. Comparison of experimentally determined and mathematically predicted percutaneous penetration rates of chemicals. Arch Toxicol, 2012, 86: 423-430.

[118] Kuczewski M, Schirmer E, Lain B, Zarbis-Papastoitsis G. A single-use purification process for the production of a monoclonal antibody produced in a PER.C6 human cell line. Biotechnol J, 2011, 6: 56-65.

[119] Kumar YR, Kumar P, Prasad M, Radhika A, Edara AC. Occupational inhalation of aniline fumes induced methemoglobinemea and hemolytic anemia precipitated days later. Indian J Occup Environ Med, 2014, 18: 95.

[120] Kuo HH, Mauk AG. Indole peroxygenase activity of indoleamine 2,3-dioxygenase. Proc Natl Acad Sci, 2012, 109: 13966-13971.

[121] Lee J-H, Lee J. Indole as an intercellular signal in microbial communities. FEMS Microbiol Rev, 2010, 34: 426-444.

[122] LEE CR, LEE JH, PARK M, PARK KS, BAE IK, KIM YB, CHA CJ, JEONG BC, LEE SH (2017) Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options. Front Cell Infect Microbiol 7:55

[123] Lee SY, Park JH, Jang SH, Nielsen LK, Kim J, Jung KS. Fermentative butanol production by Clostridia. Biotechnol Bioeng, 2008, 101: 209-228.

[124] Lee J, Kim J, Song JE, Song W-S, Kim E-J, Kim Y-G, Jeong H-J, Kim HR, Choi K-Y, Kim B-G. Production of Tyrian purple indigoid dye from tryptophan in Escherichia coli. Nat Chem Biol, 2021, 17: 104-112.

[125] Leung WWF (2007) Centrifugal separations in biotechnology. Butterworth-Heinemann

[126] Leung Wallace W-F. (2020). Selection and sizing of centrifuges. 2nd Edition, Elsevier. https://doi.org/10.1016/B978-0-08-102634-2.00009-X

[127] Li Q-S, Schwaneberg U, Fischer P, Schmid RD. Directed evolution of the fatty-acid hydroxylase P450 BM-3 into an indole-hydroxylating catalyst. Chem Eur J, 2000, 6: 1531-1536.

[128] Li F, Vijayasankaran N, Shen A, Kiss R, Amanullah A. Cell culture processes for monoclonal antibody production. Mabs, 2010, 2: 466-479.

[129] Li X, Zhang G, Zhao X, Zhou J, Du G, Chen J. A conceptual air-lift reactor design for large scale animal cell cultivation in the context of in vitro meat production. Chem Eng Sci, 2020, 211.

[130] Likidis Z, Schügerl K. Recovery of penicillin by reactive extraction in centrifugal extractors: Recovery Of Penicillin By Reactive Extraction. Biotechnol Bioeng, 1987, 30: 1032-1040.

[131] Lim HK, Chung EJ, Kim J-C, Choi GJ, Jang KS, Chung YR, Cho KY, Lee S-W. Characterization of a forest soil metagenome clone that confers indirubin and indigo production on Escherichia coli. Appl Environ Microbiol, 2005, 71: 7768-7777.

[132] Liu Y, Wang S, Wang Z, Yao Q, Fang S, Zhou X, Yuan X, Xie J. The in situ synthesis of silver nanoclusters inside a bacterial cellulose hydrogel for antibacterial applications. J Mater Chem B Mater Biol Med, 2020, 8: 4846-4850.

[133] Lodish H, Berk A, Zipursky S, Matsudaira P, Baltimore D, Darnell J. Purifying, detecting, and characterizing proteins, 2000, New York: WH Freeman.

[134] Lohtander T, Durandin N, Laaksonen T, Arola S, Laaksonen P. Stabilization of natural and synthetic indigo on nanocellulose network—towards bioactive materials and facile dyeing processes. J Clean Prod, 2021, 328.

[135] Lončar N, van Beek HL, Fraaije MW. Structure-based redesign of a self-sufficient flavin-containing monooxygenase towards indigo production. Int J Mol Sci, 2019, 20: 6148.

[136] Ma Q, Zhang X, Qu Y. Biodegradation and biotransformation of Indole: advances and perspectives. Front Microbiol, 2018, 9: 2625-2625.

[137] Marcellin E, Nielsen LK. Advances in analytical tools for high throughput strain engineering. Curr Opin Biotechnol, 2018, 54: 33-40.

[138] Marichal-Gallardo PA, Alvarez MM. State-of-the-art in downstream processing of monoclonal antibodies: process trends in design and validation. Biotechnol Prog, 2012, 28: 899-916.

[139] McClay K, Boss C, Keresztes I, Steffan RJ. Mutations of toluene-4-monooxygenase that alter regiospecificity of indole oxidation and lead to production of novel indigoid pigments. Appl Environ Microbiol, 2005, 71: 5476-5483.

[140] Mcfarlane J, Tsouris C, Birdwell JF, Schuh DL, Jennings HL, Palmer Boitrago AM, Terpstra SM. Production of biodiesel at the kinetic limit in a centrifugal reactor/separator. Ind Eng Chem Res, 2010, 49: 3160-3169.

[141] Meikrantz DH, Macaluso LL, Flim WD, Heald CJ, Mendoza G, Meikrantz SB. A new annular centrifugal contactor for pharmaceutical processes. Chem Eng Commun, 2002, 189: 1629-1639.

[142] Meraj S, Saeeda N. Effective process optimization of Indigo rope dyeing: a case study. JNTM, 2016, 6: 33-37.

[143] Mermod N, Harayama S, Timmis KN. New route to bacterial production of Indigo. Bio/technology, 1986, 4: 321-324.

[144] Meyer H-P, Minas W, Schmidhalter D. Industrial-scale fermentation. Ind Biotechnol, 2017

[145] Monti D, Ottolina G, Carrea G, Riva S. Redox reactions catalyzed by isolated enzymes. Chem Rev, 2011, 111: 4111-4140.

[146] Motschi H. ETAD’s advocacy for cost-effective regulations and compliance. Surf Coat Int Part B Coat Trans, 2003, 86: 31-34.

[147] Muhammad NIS, Rosentrater KA. Techno-economic evaluation of food waste fermentation for value-added products. Energies (basel), 2020, 13: 436.

[148] Münzberg S, Vu TG, Seidel-Morgenstern A. Generalizing countercurrent processes: distillation and beyond. Chem Ing Tec, 2018, 90: 1769-1781.

[149] Murdock D, Ensley BD, Serdar C, Thalen M. Construction of metabolic operons catalyzing the de novo biosynthesis of Indigo in Escherichia coli. Bio/technology, 1993, 11: 381-386.

[150] Nabais AMA, Cardoso JP. Ultrafiltration of fermented broths and solvent extraction of antibiotics. Bioprocess Eng, 1995, 13: 215-221.

[151] Nagayama H, Sugawara T, Endo R, Ono A, Kato H, Ohtsubo Y, Nagata Y, Tsuda M. Isolation of oxygenase genes for indigo-forming activity from an artificially polluted soil metagenome by functional screening using Pseudomonas putida strains as hosts. Appl Microbiol Biotechnol, 2015, 99: 4453-4470.

[152] Nakamura CE, Whited GM. Metabolic engineering for the microbial production of 1,3-propanediol. Curr Opin Biotechnol, 2003, 14: 454-459.

[153] Namgung S, Park HA, Kim J, Lee P-G, Kim B-G, Yang Y-H, Choi K-Y. Ecofriendly one-pot biosynthesis of indigo derivative dyes using CYP102G4 and PrnA halogenase. Dyes Pigm, 2019, 162: 80-88.

[154] Nandi S, Kwong AT, Holtz BR, Erwin RL, Marcel S, McDonald KA. Techno-economic analysis of a transient plant-based platform for monoclonal antibody production. Mabs, 2016, 8: 1456-1466.

[155] Narayanan H, Luna MF, Stosch M, . Bioprocessing in the digital age: the role of process models. Biotechnol J, 2020, 15: 1900172.

[156] Nesbeth DN, Perez-Pardo M-A, Ali S, Ward J, Keshavarz-Moore E. Growth and productivity impacts of periplasmic nuclease expression in an Escherichia coli Fab' fragment production strain. Biotechnol Bioeng, 2012, 109: 517-527.

[157] Nordlund I, Powlowski J, Shingler V. Complete nucleotide sequence and polypeptide analysis of multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600. J Bacteriol, 1990, 172: 6826-6833.

[158] Northeast Biomanufacturing Center and Collaborative (Nbc2) (2016) Downstream Processing. Introduction to Biomanufacturing. [Online] Available: https://biomanufacturing.org/curriculum-resources/program-units/downstream-processin. Accessed 20 Dec 2023

[159] Nour AH, Mohammed F, Yunus RM, Arman A. Demulsification of virgin coconut oil by centrifugation method: a feasibility study. Int J Chem Technol, 2009, 1: 59-64.

[160] Nugent DY, Ajioka J (2016) Method of dyeing fabric using microorganisms. US patent application EP16723798.1A.

[161] NURAH TO, WMADB F, RANIL C, ISONA G, VIJAY J (2017) Effect of extraction techniques on the quality of coconut oil. African J Food Sci 11:58–66

[162] ÖGMUNDARSON Ó, SUKUMARA S, HERRGÅRD MJ, FANTKE P (2020) Combining Environmental and Economic Performance for Bioprocess Optimization. Trends Biotech 38:1203–1214

[163] Olsson L, Rugbjerg P, . Robustness: linking strain design to viable bioprocesses. Trends Biotechnol , 2022, 40: 918-931.

[164] Ottaviano FG, Handy DE, Loscalzo J. Redox regulation in the extracellular environment. Circ J, 2008, 72: 1-16.

[165] Panis G, Carreon JR. Commercial astaxanthin production derived by green alga Haematococcus pluvialis: a microalgae process model and a techno-economic assessment all through production line. Algal Res (amsterdam), 2016, 18: 175-190.

[166] Parales RE, Lee K, Resnick SM, Jiang H, Lessner DJ, Gibson DT. Substrate Specificity of Naphthalene Dioxygenase: Effect of Specific Amino Acids at the Active Site of the Enzyme. J Bacteriol, 2000, 182: 1641-1649.

[167] Park J (2013) The standardising, evaluation, selection and quality control of dyes [Online]. Textile Today Bangladesh.

[168] Park J, Shore J. Significance of dye research and development for practical dyers. Color Technol, 2007, 123: 209-216.

[169] Pathak H, Madamwar D. Biosynthesis of Indigo dye by newly isolated naphthalene-degrading strain Pseudomonas sp. hob1 and its application in dyeing cotton fabric. Appl Biochem Biotechnol, 2010, 160: 1616-1626.

[170] Patnaik R, Liao JC. Engineering of Escherichia coli central metabolism for aromatic metabolite production with near theoretical yield. Appl Environ Microbiol, 1994, 60: 3903-3908.

[171] Pattanaik L, Naik SN, Hariprasad P. Valorization of waste Indigofera tinctoria L. biomass generated from indigo dye extraction process—potential towards biofuels and compost. Biomass Conv Bioref, 2019, 9: 445-457.

[172] Paul R. Denim: manufacture, finishing and applications, 2015, Cambridge: Woodhead Publishing.

[173] Paul RB, Richard; Bechtold, Thomas 2021. Indigo and Indigo Colorants. Ullmann's Encyclopedia of Industrial Chemistry. Wiley. https://doi.org/10.1002/14356007.a14_149

[174] Pazmiño DET, Snajdrova R, Rial DV, Mihovilovic MD, Fraaije MW. Altering the substrate specificity and enantioselectivity of phenylacetone monooxygenase by structure-inspired enzyme redesign. Adv Synth Catal, 2007, 349: 1361-1368.

[175] PETRIDES D, CARMICHAEL D, SILETTI C, KOULOURIS A (2019) Bioprocess Simulation and Economics. In: BERENJIAN A (ed.) Essentials in Fermentation Technology. Cham: Springer International Publishing

[176] Pfleger J (1901) Process of making indoxyl derivatives. US patent application US6755801A.

[177] PILI (2021). Q&A [Online]. https://www.pili.bio/8/qa. Accessed 24 May 2021.

[178] Pollock J, Ho SV, Farid SS. Fed-batch and perfusion culture processes: Economic, environmental, and operational feasibility under uncertainty. Biotechnol Bioeng, 2013, 110: 206-219.

[179] Pushpavanam S, Malengier B (2012) Comparison of Co-Current and Counter-Current Flow Fields on Extraction Performance in Micro-Channels. Adv Chem Eng Sci 2:309–320. https://doi.org/10.4236/aces.2012.22036

[180] Ratcliffe E, Thomas RJ, Williams DJ. Current understanding and challenges in bioprocessing of stem cell-based therapies for regenerative medicine. Br Med Bull, 2011, 100: 137-155.

[181] Rathore AS, Kateja N, Kumar D. Process integration and control in continuous bioprocessing. Curr Opin Chem Eng, 2018, 22: 18-25.

[182] Rayat AC, Chatel A, Hoare M, Lye GJ. Ultra scale-down approaches to enhance the creation of bioprocesses at scale: impacts of process shear stress and early recovery stages. Curr Opin Chem Eng, 2016, 14: 150-157.

[183] Renata H, Wang ZJ, Arnold FH. Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution. Angew Chem Int Ed, 2015, 54: 3351-3367.

[184] Robinson C, Matos CFRO, Beck D, Ren C, Lawrence J, Vasisht N, Mendel S. Transport and proofreading of proteins by the twin-arginine translocation (Tat) system in bacteria. Biochem Biophys Acta, 2011, 1808: 876-884.

[185] Rüffer N, Heidersdorf U, Kretzers I, Sprenger G, Raeven L, Takors R. Fully integrated L-phenylalanine separation and concentration using reactive-extraction with liquid-liquid centrifuges in a fed-batch process with E. coli. Bioprocess Biosyst Eng, 2004, 26: 239-248.

[186] Rywińska A, Rymowicz W. High-yield production of citric acid by Yarrowia lipolytica on glycerol in repeated-batch bioreactors. J Ind Microbiol Biotechnol, 2010, 37: 431-435.

[187] Salzillo T, D’Agostino S, Rivalta A, Giunchi A, Brillante A, . Structural, spectroscopic, and computational characterization of the concomitant polymorphs of the natural semiconductor indigo. J Phys Chem C, 2018, 122: 18422-18431.

[188] SCHMIDT H (1997) Indigo - 100 years of industrial synthesis. Weinheim

[189] Schimper CB, Ibanescu C, Bechtold T. Surface activation of dyed fabric for cellulase treatment, 2011, New York: Wiley Online Library

[190] Schofield DM, Templar A, Newton J, Nesbeth DN. Promoter engineering to optimize recombinant periplasmic Fab′ fragment production in Escherichia coli. Biotechnol Prog, 2016, 32: 840-847.

[191] Schügerl K. Solvent extraction in biotechnology: recovery of primary and secondary metabolites, 2013, Berlin: Springer Science & Business Media.

[192] Scott A. Cutting out textile pollution. Chem Eng News, 2015, 93: 18-19.

[193] Serdar CM, Douglas M, Ensley C, Burt D (1989) Enhancement of naphthalene dioxygenase activity during microbial indigo production. European Patent Application: EP0437579A1

[194] Sofer G (Ed.) (2005) Process Validation in Manufacturing of Biopharmaceuticals: Guidelines, Current Practices, and Industrial Case Studies (2nd ed.). CRC https://doi.org/10.1201/9780849398582

[195] Shi Y, Zhang L, Wang L, Li S, Qiu Z, Ding X, Wang Y. Quality blues: traditional knowledge used for natural indigo identification in southern China. J Ethnobiol Ethnomed, 2021, 17: 1-14.

[196] Shriver JA, Kaller KS, Kinsey AL, Wang KR, Sterrenberg SR, van Vors MK, Cheek JT, Horner JS. A tunable synthesis of indigoids: targeting indirubin through temperature. RSC Adv, 2022, 12: 5407-5414.

[197] Sigma-Aldrich (2022) Product Catalogue [Online]. https://www.sigmaaldrich.com/technical-service-home/product-catalog.html. Accessed 03 Jul 2022.

[198] Singh A, Chauhan NS, Thulasiram H, Taneja V, Sharma R. Identification of two flavin monooxygenases from an effluent treatment plant sludge metagenomic library. Biores Technol, 2010, 101: 8481-8484.

[199] St Clair K. The secret lives of colour, 2016, London: John Murray.

[200] Stephen MH. Chapter 2—process evaluation, 2018, 6, Amsterdam: Elsevier Inc.

[201] Tan NS, Ho B, Ding JL. Engineering a novel secretion signal for cross-host recombinant protein expression. Protein Eng, 2002, 15: 337-345.

[202] Tarleton S, Wakeman R. Solid/liquid separation: equipment selection and process design, 2006, Amsterdam: Elsevier.

[203] Textiletuts (2021) Denim Dyeing with indigo dyes [Online]. https://textiletuts.com/denim-dyeing-with-indigo-dyes/. Accessed 16 Dec 2021.

[204] Thermo Fisher Scientific (2022) Product Categories [Online]. https://www.thermofisher.com/uk/en/home/order.html. Accessed 03 Jul 2022.

[205] The Sustainable Angle (2019) Sustainable Denim Production: An Interview with Advanced Denim. Interview with Enrico Forin. Available: https://thesustainableangle.org/sustainable-denim-production-interview-with-advance-denim-mill/. Accessed 05 Aug 2021.

[206] Toprak T, Anis P. Textile industry’s environmental effects and approaching cleaner production and sustainability, an overview. J Textile Engineering & Fashion Technology, 2017, 2: 429-442.

[207] Tsagkari M, Kokossis A, Dubois JL. A method for quick capital cost estimation of biorefineries beyond the state of the art. Biofuels Bioprod Biorefin, 2020, 14: 1061-1088.

[208] Ullrich R, Poraj-Kobielska M, Herold-Majumdar OM, Vind J, Hofrichter M. Synthesis of indigo-dyes from indole derivatives by unspecific peroxygenases and their application for in-situ dyeing. Catalysts, 2021, 11: 1495.

[209] Urlacher VB, Schmid RD. Recent advances in oxygenase-catalyzed biotransformations. Curr Opin Chem Biol, 2006, 10: 156-161.

[210] U.S. HSDB (1993). Hazardous substances data bank National toxicology information program, National library of medicine, Bethesda, MD, . National Toxicology Information Program. National Library of Medicine: Department of Health and Human Services.

[211] van Hellemond EW, Janssen DB, Fraaije MW. Discovery of a novel styrene monooxygenase originating from the metagenome. Appl Environ Microbiol, 2007, 73: 5832-5839.

[212] Vandenabeele P, Moens L. Micro-Raman spectroscopy of natural and synthetic indigo samples. Analyst, 2003, 128: 187-193.

[213] Wang G, Chu J, Noorman H, Xia J, Tang W, Zhuang Y, Zhang S. Prelude to rational scale-up of penicillin production: a scale-down study. Appl Microbiol Biotechnol, 2014, 98: 2359-2369.

[214] Wang G, Tang W, Xia J, Chu J, Noorman H, van Gulik WM. Integration of microbial kinetics and fluid dynamics toward model-driven scale-up of industrial bioprocesses. Eng Life Sci, 2015, 15: 20-29.

[215] Warren L (2019) A German consumer magazine claims women’s jeans are dirty but denim industry disagrees [Online]. The Sourcing Journal. https://sourcingjournal.com/denim/denim-business/oko-test-magazine-womens-jeans-dirty-chemicals-industry-disagrees-levis-boyish-16833. Accessed 24 Aug 2022

[216] Warren L (2020) Tests show dystar’s denim dyeing process is environmentally sound [Online]. The Sourcing Journal. https://sourcingjournal.com/denim/denim-innovations/dystar-cadira-denim-system-clean-indigo-hydrosulphite-water-207204/. Accessed 05 Aug 2021

[217] Wenner N, Forkin M (2017) Indigo: sources, processes and possibilities for bioregional blue [Online]. http://fibershed.org/wp-content/uploads/2017/08/indigo-sources-processes-possibilities-june2017.pdf. Accessed 05 Aug 2021

[218] Weyler WD, Dodge TC, Lauff TJ, Wendt D (2001) Microbial production of indigo. US patent application 005866396A

[219] Wolf L. What’s that stuff?. Blue Jeans Chem Eng News, 2011, 89: 44.

[220] Woo H-J, Sanseverino J, Cox CD, Robinson KG, Sayler GS. The measurement of toluene dioxygenase activity in biofilm culture of Pseudomonas putida F1. J Microbiol Methods, 2000, 40: 181-191.

[221] Wu S, Snajdrova R, Moore JC, Baldenius K, Bornscheuer UT. Biocatalysis: enzymatic synthesis for industrial applications. Angew Chem Int Ed, 2021, 60: 88-119.

[222] Xia J, Wang G, Lin J, Wang Y, Chu J, Zhuang Y, Zhang S. Advances and practices of bioprocess scale-up, 2015, Berlin Heidelberg: Springer

[223] Yin H, Chen H, Yan M, Li Z, Yang R, Li Y, Wang Y, Guan J, Mao H, Wang Y, Zhang Y. Efficient Bioproduction of Indigo and Indirubin by Optimizing a Novel Terpenoid Cyclase XiaI in Escherichia coli. ACS Omega, 2021, 6: 20569-20576.

[224] Zou X, Xia J-Y, Chu J, Zhuang Y-P, Zhang S-L. Real-time fluid dynamics investigation and physiological response for erythromycin fermentation scale-up from 50 L to 132 m3 fermenter. Bioprocess Biosyst Eng, 2012, 35: 789-800.

Funding

Royal Academy of Engineering(ELS\25\497)

Biotechnology and Biological Sciences Research Council(BB/L007444/1)