Biosynthesis of 5‐deoxyflavanones in microorganisms

Abstract

Flavanones are the common precursors of plant polyphenolic compounds collectively known as flavonoids. Leguminous plants have evolved a distinct class of flavanone molecules, known as 5-deoxyflavanones that play important roles in their symbiotic interactions. A four-step metabolic circuit was constructed in Escherichia coli with plant genes from heterologous origins: 4-coumarate:coenzyme A ligase from Petroselinum crispum, chalcone synthases (CHS) from Medicago sativa and Petunia x hybrida and chalcone reductase and chalcone isomerase from M. sativa. Evaluation of the different recombinant strains in shake flask experiments demonstrated that P. hybrida rather than M. sativa CHS resulted in the highest liquiritigenin production levels in glucose minimal medium, starting from precursor p-coumaric acid. Expression of the same recombinant pathway in Saccharomyces cerevisiae resulted in the accumulation of both 5-hydroxyflavanone and 5-deoxyflavanone, with the yields of the later lower than that achieved in E. coli. Other phenylpropanoid acid precursors, such as cinnamic acid and caffeic acid could also be metabolized through the recombinant pathway, yielding corresponding 5-deoxyflavanone compounds. The construction of such recombinant strains for 5-deoxyflavanone biosynthesis offers an alternative way to biochemically characterize flavonoid biosynthetic enzymes and promising production platforms for the biosynthesis of such high-value natural products.

Combinatorial Biosynthesis of Non-bacterial and Unnatural Flavonoids, Stilbenoids and Curcuminoids by Microorganisms

“…Our success in fermentative production of plant-specific polyketides by E. coli carrying an artificially assembled phenylpropanoid pathway was the first example to show that a nearly complete biosynthetic pathway in plants was established in a heterologous microorganism for production of flavanones from the amino acid precursors, phenylalanine and tyrosine [5,6]. Later, Yan et al [7] produced 5-deoxyflavanones in E. coli and Beekwilder et al [8] produced a natural raspberry ketone in E. coli. The approach of this type of combining genes from different organisms and designing a gene cluster to produce a bioactive compound leads not only to diversification of both chemical and natural product libraries but also to efficient use of the potential of the host organisms, particularly when microorganisms are used as the hosts.…”

A Novel Muconic Acid Biosynthesis Approach by Shunting Tryptophan Biosynthesis via Anthranilate

“…Among all developed alternatives, microbial synthesis has been proven to be competent and promising. So far, a variety of chemicals, including biofuels, amino acids, and plant secondary metabolites, have been produced by metabolically engineered microorganisms (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

In vitro Fertilization with Mouse Sperm Activated by Components of Licorice Root Extract

“…We also found that the hydrolysis of diarylheptanoid glycoside to free diarylheptanoid in culture medium has anti-trypanosomal and apoptotic activities [27], suggesting that isoliquiritigenin is a liquiritigenin precursor. In fact the biosynthetic pathway between isoliquiritigenin to formononetin via liquiritigenin starting from cinnamic acid was confirmed using microorgainisms and G. echinata cell-free system, respectively as shown in Figure 8 [28,29].…”