Production of plant-derived polyphenols in microorganisms: current state and perspectives

Abstract

Plants synthesize several thousand different polyphenols of which many have the potential to aid in preventing or treating cancer, cardiovascular, and neurodegenerative diseases. However, plants usually contain complex polyphenol mixtures impeding access to individual compounds in larger quantities. In contrast, functional integration of biosynthetic plant polyphenol pathways into microorganisms allows for the production of individual polyphenols as chemically distinct compounds, which can be synthesized in large amounts and can be more easily isolated. Over the last decade, microbial synthesis of many plant polyphenols could be achieved, and along the way, many decisive bottlenecks in the endogenous microbial host metabolism as well as in the heterologous plant pathways could be identified. In this review, we present recent advancements in metabolic engineering of microorganisms for the production of plant polyphenols and discuss how current challenges could be addressed in the future.

Modulation of the central carbon metabolism of Corynebacterium glutamicum improves malonyl‐CoA availability and increases plant polyphenol synthesis

“…When comparing microbial resveratrol and naringenin production in C. glutamicum , E. coli or S. cerevisiae , either from supplemented precursors or directly from glucose, resveratrol titers generally seem to exceed the ones of naringenin independent from the utilized host or the heterologous genes used (Chouhan, Sharma, Zha, Guleria, & Koffas, ; Jeandet et al, ; Milke et al, ). Similar observations have also been made for two very similar E. coli strains also engineered towards naringenin and resveratrol synthesis (Yang et al, ).…”

“…Unfortunately, plants produce polyphenols only at very low rates and the overall polyphenol content is always subject to incalculable seasonal and climatic variations. Microorganisms, genetically engineered for plant polyphenol production, represent a promising alternative for the production of these valuable compounds (Milke, Aschenbrenner, Marienhagen, & Kallscheuer, ). However, tight regulation of the endogenous malonyl‐CoA synthesis with the aim to maintain only low levels of this fatty acid precursor in microorganisms, turned out to be the decisive bottleneck during microbial polyphenol production utilizing Escherichia coli and Saccharomyces cerevisiae (Kim & Ahn, ; Leonard, Lim, Saw, & Koffas, ; M. Li, Schneider, Kristensen, Borodina, & Nielsen, ; Lim, Fowler, Hueller, Schaffer, & Koffas, ; Yang, Lin, Li, Linhardt, & Yan, ).…”

Engineering Lactococcus lactis for the production of unusual anthocyanins using tea as substrate

“…Many plant pathways have been successfully reconstructed and expressed in microorganisms so far. However, almost all of them employed Escherichia coli and Saccharomyces cerevisiae as production hosts (Marienhagen and Bott, 2013;Milke et al, 2018). Lactic acid bacteria, and in particular L. lactis, provide an attractive alternative for production of plant high value chemicals.…”

Microbial Production of Natural and Unnatural Monolignols with Escherichia coli

“…General precursor molecules of these valuable compounds are phenylpropanoids, which in turn are derived from the aromatic amino acids l ‐phenylalanine or l ‐tyrosine ( 1 , Scheme ). Phenylpropanoid synthesis starts with the non‐oxidative deamination of the aromatic amino acid to yield the typical phenylpropanoid core structure: a phenyl group attached to a propene tail . This decisive reaction is catalyzed by ammonia lyases: either phenylalanine ammonia lyases (PALs) or tyrosine ammonia lyases (TALs).…”