Cho, J. S., Kim, G. B., Eun, H., Moon, C. W. & Lee, S. Y. Designing microbial cell factories for the production of chemicals. JACS Au 2, 1781–1799 (2022).
Cravens, A., Payne, J. & Smolke, C. D. Synthetic biology strategies for microbial biosynthesis of plant natural products. Nat. Commun. 10, 2142 (2019).
Medema, M. H., de Rond, T. & Moore, B. S. Mining genomes to illuminate the specialized chemistry of life. Nat. Rev. Genet. 22, 553–571 (2021).
Zhang, J. J., Tang, X. & Moore, B. S. Genetic platforms for heterologous expression of microbial natural products. Nat. Prod. Rep. 36, 1313–1332 (2019).
Opgenorth, P. et al. Lessons from two design–build–test–learn cycles of dodecanol production in Escherichia coli aided by machine learning. ACS Synth. Biol. 8, 1337–1351 (2019).
Choi, K. R. et al. Systems metabolic engineering strategies: integrating systems and synthetic biology with metabolic engineering. Trends Biotechnol. 37, 817–837 (2019).
Ko, Y.-S. et al. Tools and strategies of systems metabolic engineering for the development of microbial cell factories for chemical production. Chem. Soc. Rev. 49, 4615–4636 (2020).
Burgard, A. P., Pharkya, P. & Maranas, C. D. Optknock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol. Bioeng. 84, 647–657 (2003).
Fong, S. S. et al. In silico design and adaptive evolution of Escherichia coli for production of lactic acid. Biotechnol. Bioeng. 91, 643–648 (2005).
Alper, H., Jin, Y.-S., Moxley, J. F. & Stephanopoulos, G. Identifying gene targets for the metabolic engineering of lycopene biosynthesis in Escherichia coli. Metab. Eng. 7, 155–164 (2005).
Jantama, K. et al. Combining metabolic engineering and metabolic evolution to develop nonrecombinant strains of Escherichia coli C that produce succinate and malate. Biotechnol. Bioeng. 99, 1140–1153 (2008).
Otero, J. M. et al. Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory. PLoS ONE 8, e54144 (2013).
Klamt, S. & Mahadevan, R. On the feasibility of growth-coupled product synthesis in microbial strains. Metab. Eng. 30, 166–178 (2015).
von Kamp, A. & Klamt, S. Growth-coupled overproduction is feasible for almost all metabolites in five major production organisms. Nat. Commun. 8, 15956 (2017).
Banerjee, D. et al. Genome-scale metabolic rewiring improves titers rates and yields of the non-native product indigoidine at scale. Nat. Commun. 11, 5385 (2020).
Yim, H. et al. Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat. Chem. Biol. 7, 445–452 (2011).
Dinh, H. V., King, Z. A., Palsson, B. O. & Feist, A. M. Identification of growth-coupled production strains considering protein costs and kinetic variability. Metab. Eng. Commun. 7, e00080 (2018).
Cicchillo, R. M. et al. An unusual carbon–carbon bond cleavage reaction during phosphinothricin biosynthesis. Nature 459, 871–874 (2009).
Patteson, J. B. et al. Biosynthesis of fluopsin C, a copper-containing antibiotic from Pseudomonas aeruginosa. Science 374, 1005–1009 (2021).
Hagel, J. & Facchini, P. Biochemistry and occurrence of O-demethylation in plant metabolism. Front. Physiol. https://doi.org/10.3389/fphys.2010.00014 (2010).
Augustin, M. M., Augustin, J. M., Brock, J. R. & Kutchan, T. M. Enzyme morphinan N-demethylase for more sustainable opiate processing. Nat. Sustain. 2, 465–474 (2019).
Soohoo, A. M., Cogan, D. P., Brodsky, K. L. & Khosla, C. Structure and mechanisms of assembly-line polyketide synthases. Annu. Rev. Biochem. 93, 471–498 (2024).
Chen, F. Y.-H., Jung, H.-W., Tsuei, C.-Y. & Liao, J. C. Converting Escherichia coli to a synthetic methylotroph growing solely on methanol. Cell 182, 933–946.e14 (2020).
Kim, S. et al. Growth of E. coli on formate and methanol via the reductive glycine pathway. Nat. Chem. Biol. 16, 538–545 (2020).
Jiang, W. et al. Metabolic engineering strategies to enable microbial utilization of C1 feedstocks. Nat. Chem. Biol. 17, 845–855 (2021).
Figon, F. & Casas, J. Ommochromes in invertebrates: biochemistry and cell biology. Biol. Rev. 94, 156–183 (2019).
Kumar, A., Williams, T. L., Martin, C. A., Figueroa-Navedo, A. M. & Deravi, L. F. Xanthommatin-based electrochromic displays inspired by nature. ACS Appl. Mater. Interfaces 10, 43177–43183 (2018).
Martin, C. L. et al. Color-changing paints enabled by photoresponsive combinations of bio-inspired colorants and semiconductors. Adv. Sci. 10, 2302652 (2023).
Sullivan, P. A., Wilson, D. J., Vallon, M., Bower, D. Q. & Deravi, L. F. Inkjet printing bio-inspired electrochromic pixels. Adv. Mater. Interfaces 10, 2202463 (2023).
Wilson, D. J., MartÃn-MartÃnez, F. J. & Deravi, L. F. Wearable light sensors based on unique features of a natural biochrome. ACS Sens 7, 523–533 (2022).
Martin, C. A. et al. Biomimetic colorants and coatings designed with cephalopod-inspired nanocomposites. ACS Appl. Bio Mater. 4, 507–513 (2021).
A. Martin, C. et al. A bioinspired, photostable UV-filter that protects mammalian cells against UV-induced cellular damage. Chem. Commun. 55, 12036–12039 (2019).
Deravi, L. F., Cui, I. & Martin, C. A. Using cephalopod-inspired chemistry to extend long-wavelength ultraviolet and visible light protection of mineral sunscreens. Int. J. Cosmet. Sci. 46, 941–948 (2024).
Riou, M. & Christidès, J.-P. Cryptic color change in a crab spider (Misumena vatia): identification and quantification of precursors and ommochrome pigments by HPLC. J. Chem. Ecol. 36, 412–423 (2010).
Williams, T. L. et al. Dynamic pigmentary and structural coloration within cephalopod chromatophore organs. Nat. Commun. 10, 1004 (2019).
Figon, F. et al. Uncyclized xanthommatin is a key ommochrome intermediate in invertebrate coloration. Insect Biochem. Mol. Biol. 124, 103403 (2020).
Forman, K. A. & Thulin, C. D. Ommochrome wing pigments in the monarch butterfly Danaus plexippus (Lepidoptera: Nymphalidae). J. Insect Sci. 22, 12 (2022).
Huang, G., Song, L., Du, X., Huang, X. & Wei, F. Evolutionary genomics of camouflage innovation in the orchid mantis. Nat. Commun. 14, 4821 (2023).
Butenandt, A., Schiedt, U. & Biekert, E. Über ommochrome, III. Synthese des xanthommatins. J. Liebigs Ann. Chem. 588, 106–116 (1954).
Nikel, P. I. & de Lorenzo, V. Pseudomonas putida as a functional chassis for industrial biocatalysis: from native biochemistry to trans-metabolism. Metab. Eng. 50, 142–155 (2018).
Turlin, J., Dronsella, B., De Maria, A., Lindner, S. N. & Nikel, P. I. Integrated rational and evolutionary engineering of genome-reduced Pseudomonas putida strains promotes synthetic formate assimilation. Metab. Eng. 74, 191–205 (2022).
Buchanan, J. L., Rauckhorst, A. J. & Taylor, E. B. 3-hydroxykynurenine is a ROS-inducing cytotoxic tryptophan metabolite that disrupts the TCA cycle. Preprint at bioRxiv https://doi.org/10.1101/2023.07.10.548411 (2023).
Lewis-Luján, L. M. et al. Inhibition of pathogenic bacteria and fungi by natural phenoxazinone from octopus ommochrome pigments. J. Microbiol. Biotechnol. 32, 989–1002 (2022).
Kurnasov, O. et al. Aerobic tryptophan degradation pathway in bacteria: novel kynurenine formamidase. FEMS Microbiol. Lett. 227, 219–227 (2003).
Kurnasov, O. et al. NAD biosynthesis: identification of the tryptophan to quinolinate pathway in bacteria. Chem. Biol. 10, 1195–1204 (2003).
Matthijs, S. et al. The Pseudomonas siderophore quinolobactin is synthesized from xanthurenic acid, an intermediate of the kynurenine pathway. Mol. Microbiol. 52, 371–384 (2004).
Le Roes-Hill, M., Goodwin, C. & Burton, S. Phenoxazinone synthase: what’s in a name? Trends Biotechnol. 27, 248–258 (2009).
Hughes, M. A., Baggs, M. J., al-Dulayymi, J., Baird, M. S. & Williams, P. A. Accumulation of 2-aminophenoxazin-3-one-7-carboxylate during growth of Pseudomonas putida TW3 on 4-nitro-substituted substrates requires 4-hydroxylaminobenzoate lyase (PnbB). Appl. Environ. Microbiol. 68, 4965–4970 (2002).
Yue, S.-J. et al. Synthesis of cinnabarinic acid by metabolically engineered Pseudomonas chlororaphis GP72. Biotechnol. Bioeng. 116, 3072–3083 (2019).
Christen, S., Southwell-Keely, P. T. & Stocker, R. Oxidation of 3-hydroxyanthranilic acid to the phenoxazinone cinnabarinic acid by peroxyl radicals and by compound I of peroxidases or catalase. Biochemistry 31, 8090–8097 (1992).
MartÃnez-GarcÃa, E., Nikel, P. I., Aparicio, T. & de Lorenzo, V. Pseudomonas 2.0: genetic upgrading of P. putida KT2440 as an enhanced host for heterologous gene expression. Microb. Cell Fact. 13, 159 (2014).
Yishai, O., Goldbach, L., Tenenboim, H., Lindner, S. N. & Bar-Even, A. Engineered assimilation of exogenous and endogenous formate in Escherichia coli. ACS Synth. Biol. 6, 1722–1731 (2017).
Marx, C. J., Laukel, M., Vorholt, J. A. & Lidstrom, M. E. Purification of the formate-tetrahydrofolate ligase from Methylobacterium extorquens AM1 and demonstration of its requirement for methylotrophic growth. J. Bacteriol. 185, 7169–7175 (2003).
Nogales, J. et al. High-quality genome-scale metabolic modelling of Pseudomonas putida highlights its broad metabolic capabilities. Environ. Microbiol. 22, 255–269 (2020).
Alter, T. B. & Ebert, B. E. Determination of growth-coupling strategies and their underlying principles. BMC Bioinformatics 20, 447 (2019).
Alter, T. B. et al. Metabolic growth-coupling strategies for in vivo enzyme selection systems. Metab. Eng. Commun. 20, e00257 (2025).
Claassens, N. J. et al. Replacing the Calvin cycle with the reductive glycine pathway in Cupriavidus necator. Metab. Eng. 62, 30–41 (2020).
Wirth, N. T., Kozaeva, E. & Nikel, P. I. Accelerated genome engineering of Pseudomonas putida by I-SceI-mediated recombination and CRISPR–Cas9 counterselection. Microb. Biotechnol. 13, 233–249 (2020).
Volke, D. C., Friis, L., Wirth, N. T., Turlin, J. & Nikel, P. I. Synthetic control of plasmid replication enables target- and self-curing of vectors and expedites genome engineering of Pseudomonas putida. Metab. Eng. Commun. 10, e00126 (2020).
Volke, D. C., Wirth, N. T. & Nikel, P. I. Rapid genome engineering of Pseudomonas assisted by fluorescent markers and tractable curing of plasmids. Bio Protoc. 11, e3917 (2021).
Hartmans, S., Smits, J. P., van der Werf, M. J., Volkering, F. & de Bont, J. A. M. Metabolism of styrene oxide and 2-phenylethanol in the styrene-degrading Xanthobacter strain 124X. Appl. Environ. Microbiol. 55, 2850–2855 (1989).
Matthijs, S. et al. Thioquinolobactin, a Pseudomonas siderophore with antifungal and anti-Pythium activity. Environ. Microbiol. 9, 425–434 (2007).
Farrow, J. M. & Pesci, E. C. Two distinct pathways supply anthranilate as a precursor of the Pseudomonas quinolone signal. J. Bacteriol. 189, 3425–3433 (2007).
Sazinas, P., Hansen, M. L., Aune, M. I., Fischer, M. H. & Jelsbak, L. A rare thioquinolobactin siderophore present in a bioactive Pseudomonas sp. DTU12.1. Genome Biol. Evol. 11, 3529–3533 (2019).
Lane, M. C., Alteri, C. J., Smith, S. N. & Mobley, H. L. T. Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract. Proc. Natl Acad. Sci. USA 104, 16669–16674 (2007).
Sandberg, T. E., Salazar, M. J., Weng, L. L., Palsson, B. O. & Feist, A. M. The emergence of adaptive laboratory evolution as an efficient tool for biological discovery and industrial biotechnology. Metab. Eng. 56, 1–16 (2019).
Guzmán, G. I. et al. Enzyme promiscuity shapes adaptation to novel growth substrates. Mol. Syst. Biol. 15, e8462 (2019).
Phaneuf, P. V., Gosting, D., Palsson, B. O. & Feist, A. M. ALEdb 1.0: a database of mutations from adaptive laboratory evolution experimentation. Nucleic Acids Res 47, D1164–D1171 (2019).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
Orsi, E., Claassens, N. J., Nikel, P. I. & Lindner, S. N. Growth-coupled selection of synthetic modules to accelerate cell factory development. Nat. Commun. 12, 5295 (2021).
Femmer, C., Bechtold, M., Held, M. & Panke, S. In vivo directed enzyme evolution in nanoliter reactors with antimetabolite selection. Metab. Eng. 59, 15–23 (2020).
Luo, H. et al. Directed metabolic pathway evolution enables functional pterin-dependent aromatic-amino-acid hydroxylation in Escherichia coli. ACS Synth. Biol. 9, 494–499 (2020).
Luo, H. et al. Coupling S-adenosylmethionine–dependent methylation to growth: design and uses. PLoS Biol. 17, e2007050 (2019).
Lin, B. et al. Reconstitution of TCA cycle with DAOCS to engineer Escherichia coli into an efficient whole cell catalyst of penicillin G. Proc. Natl Acad. Sci. USA 112, 9855–9859 (2015).
Eggert, C., Temp, U., Dean, J. F. D. & Eriksson, K.-E. L. Laccase-mediated formation of the phenoxazinone derivative, cinnabarinic acid. FEBS Lett. 376, 202–206 (1995).
Gerhart, J. C. & Pardee, A. B. The enzymology of control by feedback inhibition. J. Biol. Chem. 237, 891–896 (1962).
Lloyd, C. J. et al. The genetic basis for adaptation of model-designed syntrophic co-cultures. PLoS Comput. Biol. 15, e1006213 (2019).
Luhavaya, H., Sigrist, R., Chekan, J. R., McKinnie, S. M. K. & Moore, B. S. Biosynthesis of L-4-chlorokynurenine, an antidepressant prodrug and a non-proteinogenic amino acid found in lipopeptide antibiotics. Angew. Chem. Int. Ed. Engl. 58, 8394–8399 (2019).
Walsh, C. T., Haynes, S. W. & Ames, B. D. Aminobenzoates as building blocks for natural product assembly lines. Nat. Prod. Rep. 29, 37–59 (2011).
Alter, T.B. Model-based simulation of growth-coupled production of xanthommatin. Zenodo https://doi.org/10.5281/zenodo.17016978 (2025).
Ebrahim, A., Lerman, J. A., Palsson, B. O. & Hyduke, D. R. COBRApy: constraints-based reconstruction and analysis for Python. BMC Syst. Biol. 7, 74 (2013).
Sandberg, T. E. et al. Evolution of Escherichia coli to 42 °C and subsequent genetic engineering reveals adaptive mechanisms and novel mutations. Mol. Biol. Evol. 31, 2647–2662 (2014).
Deatherage, D. E. & Barrick, J. E. Identification of mutations in laboratory evolved microbes from next-generation sequencing data using breseq. Methods Mol. Biol. 1151, 165–188 (2014).
The Galaxy Community The Galaxy platform for accessible, reproducible, and collaborative data analyses: 2024 update. Nucleic Acids Res. 52, W83–W94 (2024).
Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).
Danecek, P. et al. Twelve years of SAMtools and BCFtools. GigaScience 10, giab008 (2021).
Garrison, E., Kronenberg, Z. N., Dawson, E. T., Pedersen, B. S. & Prins, P. A spectrum of free software tools for processing the VCF variant call format: vcflib, bio-vcf, cyvcf2, hts-nim and slivar. PLoS Comput. Biol. 18, e1009123 (2022).
Dongol, M., El-Nahass, M. M., El-Denglawey, A., Elhady, A. F. & Abuelwafa, A. A. Optical properties of nano 5,10,15,20-tetraphenyl-21H,23H-prophyrin nickel (II) thin films. Curr. Appl. Phys. 12, 1178–1184 (2012).
Kutuzova, S. et al. SmartPeak automates targeted and quantitative metabolomics data processing. Anal. Chem. 92, 15968–15974 (2020).
