Polyphenols
are naturally produced in plants and have several biological and potential therapeutic activities such as anti inflammatory, antioxidant and anticancer They have an estimated market size of USD 2 26 billion by 2027 However, polyphenols are extracted from plants where they accumulate in low amounts over long growth periods In addition, their purification is difficult and expensive since it requires the separation of other compounds with similar chemical structures in an environmentally unfriendly process Heterologous microbial production has several benefits as it is not limited by plant availability or environmental factors and it is a renewable, environmentally friendly and sustainable approach Herein, we report the construction of artificial pathways for the production of curcuminoids and furanocoumarins using Escherichia coli as chassis These compounds can be produced from tyrosine or hydroxycinnamic acids as precursors and have in common the phenylpropanoids pathway Pure curcumin production from ferulic acid achieved 563 mg/L Curcuminoids were also produced from tyrosine 42 mg/L) using a modular pathway combining synthetic biologic and co culture engineering To our knowledge, these are the highest titers of curcuminoids obtained to date CRISPR Cas 9 was used to disrupt the lacZ gene in order to follow co culture population compositionPortuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2020 unit
and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund (ERDF) under the scope of Norte2020 -
Programa Operacional Regional do Norte. In addition, the authors acknowledge the Biomass and Bioenergy Research Infrastructure (BBRI) – LISBOA-010145-
FEDER-022059, supported by Operational Program for Competitiveness and Internationalization (PORTUGAL2020), the Lisbon Portugal Regional Operational
Program (Lisboa2020), and Norte2020 under the Portugal 2020 Partnership Agreement, through the ERDF. JR is recipient of a fellowship supported by a doctoral
advanced training (SFRH/BD/138325/2018) funded by FCTinfo:eu-repo/semantics/publishedVersio
