Manipulation of the precursor supply for high-level production of longifolene by metabolically engineered Escherichia coli

Yujin Cao, Rubing Zhang, Wei Liu, Guang Zhao, Wei Niu, Jiantao Guo, Mo Xian, Huizhou Liu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Longifolene is a naturally occurring tricyclic sesquiterpene widely used in many different fields. Up to now, this valuable terpene was mainly manufactured from the high-boiling fraction of certain pine resins. Microbial production can be a promising alternative to the extraction from natural plant sources. Here, we present the metabolic engineering strategy to assemble biosynthetic pathway for longifolene production in Escherichia coli. E. coli was rendered to produce longifolene by heterologously expressing a codon optimized longifolene synthase from Picea abies. Augmentation of the metabolic flux to farnesyl pyrophosphate (FPP) by different FPP synthases conferred a 1.8-fold increase in longifolene production. An additional enhancement of longifolene production (up to 2.64 mg/L) was achieved by introducing an exogenous mevalonate pathway. Under fed-batch conditions, the best-performing strain was able to produce 382 mg/L of longifolene in a 5 L bioreactor. These results demonstrated the feasibility of producing longifolene by microbial fermentation and could serve as the basis for the construction of more robust strains in the future.

Original languageEnglish (US)
Article number95
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Escherichia coli
Abies
Picea
Metabolic Engineering
Mevalonic Acid
longifolene
Sesquiterpenes
Biosynthetic Pathways
Terpenes
Bioreactors
Codon
Fermentation
farnesyl pyrophosphate

ASJC Scopus subject areas

  • General

Cite this

Manipulation of the precursor supply for high-level production of longifolene by metabolically engineered Escherichia coli. / Cao, Yujin; Zhang, Rubing; Liu, Wei; Zhao, Guang; Niu, Wei; Guo, Jiantao; Xian, Mo; Liu, Huizhou.

In: Scientific Reports, Vol. 9, No. 1, 95, 01.12.2019.

Research output: Contribution to journalArticle

@article{4e2de70145b4499f8bece5139cbf257f,
title = "Manipulation of the precursor supply for high-level production of longifolene by metabolically engineered Escherichia coli",
abstract = "Longifolene is a naturally occurring tricyclic sesquiterpene widely used in many different fields. Up to now, this valuable terpene was mainly manufactured from the high-boiling fraction of certain pine resins. Microbial production can be a promising alternative to the extraction from natural plant sources. Here, we present the metabolic engineering strategy to assemble biosynthetic pathway for longifolene production in Escherichia coli. E. coli was rendered to produce longifolene by heterologously expressing a codon optimized longifolene synthase from Picea abies. Augmentation of the metabolic flux to farnesyl pyrophosphate (FPP) by different FPP synthases conferred a 1.8-fold increase in longifolene production. An additional enhancement of longifolene production (up to 2.64 mg/L) was achieved by introducing an exogenous mevalonate pathway. Under fed-batch conditions, the best-performing strain was able to produce 382 mg/L of longifolene in a 5 L bioreactor. These results demonstrated the feasibility of producing longifolene by microbial fermentation and could serve as the basis for the construction of more robust strains in the future.",
author = "Yujin Cao and Rubing Zhang and Wei Liu and Guang Zhao and Wei Niu and Jiantao Guo and Mo Xian and Huizhou Liu",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-018-36495-w",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Manipulation of the precursor supply for high-level production of longifolene by metabolically engineered Escherichia coli

AU - Cao, Yujin

AU - Zhang, Rubing

AU - Liu, Wei

AU - Zhao, Guang

AU - Niu, Wei

AU - Guo, Jiantao

AU - Xian, Mo

AU - Liu, Huizhou

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Longifolene is a naturally occurring tricyclic sesquiterpene widely used in many different fields. Up to now, this valuable terpene was mainly manufactured from the high-boiling fraction of certain pine resins. Microbial production can be a promising alternative to the extraction from natural plant sources. Here, we present the metabolic engineering strategy to assemble biosynthetic pathway for longifolene production in Escherichia coli. E. coli was rendered to produce longifolene by heterologously expressing a codon optimized longifolene synthase from Picea abies. Augmentation of the metabolic flux to farnesyl pyrophosphate (FPP) by different FPP synthases conferred a 1.8-fold increase in longifolene production. An additional enhancement of longifolene production (up to 2.64 mg/L) was achieved by introducing an exogenous mevalonate pathway. Under fed-batch conditions, the best-performing strain was able to produce 382 mg/L of longifolene in a 5 L bioreactor. These results demonstrated the feasibility of producing longifolene by microbial fermentation and could serve as the basis for the construction of more robust strains in the future.

AB - Longifolene is a naturally occurring tricyclic sesquiterpene widely used in many different fields. Up to now, this valuable terpene was mainly manufactured from the high-boiling fraction of certain pine resins. Microbial production can be a promising alternative to the extraction from natural plant sources. Here, we present the metabolic engineering strategy to assemble biosynthetic pathway for longifolene production in Escherichia coli. E. coli was rendered to produce longifolene by heterologously expressing a codon optimized longifolene synthase from Picea abies. Augmentation of the metabolic flux to farnesyl pyrophosphate (FPP) by different FPP synthases conferred a 1.8-fold increase in longifolene production. An additional enhancement of longifolene production (up to 2.64 mg/L) was achieved by introducing an exogenous mevalonate pathway. Under fed-batch conditions, the best-performing strain was able to produce 382 mg/L of longifolene in a 5 L bioreactor. These results demonstrated the feasibility of producing longifolene by microbial fermentation and could serve as the basis for the construction of more robust strains in the future.

UR - http://www.scopus.com/inward/record.url?scp=85060028370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060028370&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-36495-w

DO - 10.1038/s41598-018-36495-w

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 95

ER -