Developing E. coli-E. coli co-cultures to overcome barriers of heterologous tryptamine biosynthesis

TY - JOUR

T1 - Developing E. coli-E. coli co-cultures to overcome barriers of heterologous tryptamine biosynthesis

AU - Wang, Xiaonan

AU - Policarpio, Lizelle

AU - Prajapati, Dhara

AU - Li, Zhenghong

AU - Zhang, Haoran

N1 - Publisher Copyright: © 2019 The Authors

PY - 2020/6

Y1 - 2020/6

N2 - Tryptamine is an alkaloid compound with demonstrated bioactivities and is also a precursor molecule to many important hormones and neurotransmitters. The high efficiency biosynthesis of tryptamine from inexpensive and renewable carbon substrates is of great research and application significance. In the present study, a tryptamine biosynthesis pathway was established in a metabolically engineered E. coli-E. coli co-culture. The upstream and downstream strains of the co-culture were dedicated to tryptophan provision and conversion to tryptamine, respectively. The constructed co-culture was cultivated using either glucose or glycerol as carbon source for de novo production of tryptamine. The manipulation of the co-culture strains’ inoculation ratio was adapted to balance the biosynthetic strengths of the pathway modules for bioproduction optimization. Moreover, a biosensor-assisted cell selection strategy was adapted to improve the pathway intermediate tryptophan provision by the upstream strain, which further enhanced the tryptamine biosynthesis. The resulting biosensor-assisted modular co-culture produced 194 ​mg/L tryptamine with a yield of 0.02 ​g/g glucose using shake flask cultivation. The findings of this work demonstrate that the biosensor-assisted modular co-culture engineering offers a new perspective for conducting microbial biosynthesis.

AB - Tryptamine is an alkaloid compound with demonstrated bioactivities and is also a precursor molecule to many important hormones and neurotransmitters. The high efficiency biosynthesis of tryptamine from inexpensive and renewable carbon substrates is of great research and application significance. In the present study, a tryptamine biosynthesis pathway was established in a metabolically engineered E. coli-E. coli co-culture. The upstream and downstream strains of the co-culture were dedicated to tryptophan provision and conversion to tryptamine, respectively. The constructed co-culture was cultivated using either glucose or glycerol as carbon source for de novo production of tryptamine. The manipulation of the co-culture strains’ inoculation ratio was adapted to balance the biosynthetic strengths of the pathway modules for bioproduction optimization. Moreover, a biosensor-assisted cell selection strategy was adapted to improve the pathway intermediate tryptophan provision by the upstream strain, which further enhanced the tryptamine biosynthesis. The resulting biosensor-assisted modular co-culture produced 194 ​mg/L tryptamine with a yield of 0.02 ​g/g glucose using shake flask cultivation. The findings of this work demonstrate that the biosensor-assisted modular co-culture engineering offers a new perspective for conducting microbial biosynthesis.

KW - Biosensor

KW - E. coli

KW - Modular co-culture engineering

KW - Pathway modularization

KW - Tryptamine

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U2 - 10.1016/j.mec.2019.e00110

DO - 10.1016/j.mec.2019.e00110

M3 - Article

SN - 2214-0301

VL - 10

JO - Metabolic Engineering Communications

JF - Metabolic Engineering Communications

M1 - e00110

ER -