Entdeckung neuer bakterieller Chalconisomerasen durch eine Sequenz‐Struktur‐Funktions‐Evolutions‐Strategie für die enzymatische Synthese von (<i>S</i>)‐Flavanonen

Meinert, Hannes; Dong, Yi; Zirpel, Bastian; Schuiten, Eva; Geißler, Torsten; Gross, Egon; Brückner, Stephan; Hartmann, Beate; Röttger, Carsten; Ley, Jakob P; Bornscheuer, Uwe T.

doi:10.1002/ange.202107182

“…Plant CHIs share high sequence identities and 3D structural similarities with each other, and catalyze the irreversible isomerization of chalcone into flavanones using a catalytic H 2 O‐mediated acid‐base mechanism due to the solvent‐exposed substrate‐binding site during the catalytic process (Figure S15a) [16] . Bacterial CHIs also share high sequence identities with each other, and catalyze the reversible reactions from flavanones to chalcones [17] . The physiological role of bacterial CHI is to participate in the degradation of flavanone in gut bacteria (Figure S15b,c) [18, 19] .…”

Section: Resultsmentioning

confidence: 99%

Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining

Zhang

¹

,

Zhang

²

,

Feng

³

et al. 2023

View full text Add to dashboard Cite

Flavonoids are important plant natural products with variable structures and bioactivities. All known plant flavonoids are generated under the catalysis of a type III polyketide synthase (PKS) followed by a chalcone isomerase (CHI) and a flavone synthase (FNS). In this study, the biosynthetic gene cluster of chlorflavonin, a fungal flavonoid with acetolactate synthase inhibitory activity, was discovered using a self‐resistance‐gene‐directed strategy. A novel flavonoid biosynthetic pathway in fungi was revealed. A core nonribosomal peptide synthetase‐polyketide synthase (NRPS‐PKS) is responsible for the generation of the key precursor chalcone. Then, a new type of CHI catalyzes the conversion of a chalcone into a flavanone by a histidine‐mediated oxa‐Michael addition mechanism. Finally, the desaturation of flavanone to flavone is catalyzed by a new type of FNS, a flavin mononucleotide (FMN)‐dependent oxidoreductase.

show abstract

“…Plant CHIs share high sequence identities and 3D structural similarities with each other, and catalyze the irreversible isomerization of chalcone into flavanones using a catalytic H 2 O‐mediated acid‐base mechanism due to the solvent‐exposed substrate‐binding site during the catalytic process (Figure S15a) [16] . Bacterial CHIs also share high sequence identities with each other, and catalyze the reversible reactions from flavanones to chalcones [17] . The physiological role of bacterial CHI is to participate in the degradation of flavanone in gut bacteria (Figure S15b,c) [18, 19] .…”

Section: Resultsmentioning

confidence: 99%

Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining

Zhang

¹

,

Zhang

²

,

Feng

³

et al. 2023

View full text Add to dashboard Cite

Flavonoids are important plant natural products with variable structures and bioactivities. All known plant flavonoids are generated under the catalysis of a type III polyketide synthase (PKS) followed by a chalcone isomerase (CHI) and a flavone synthase (FNS). In this study, the biosynthetic gene cluster of chlorflavonin, a fungal flavonoid with acetolactate synthase inhibitory activity, was discovered using a self‐resistance‐gene‐directed strategy. A novel flavonoid biosynthetic pathway in fungi was revealed. A core nonribosomal peptide synthetase‐polyketide synthase (NRPS‐PKS) is responsible for the generation of the key precursor chalcone. Then, a new type of CHI catalyzes the conversion of a chalcone into a flavanone by a histidine‐mediated oxa‐Michael addition mechanism. Finally, the desaturation of flavanone to flavone is catalyzed by a new type of FNS, a flavin mononucleotide (FMN)‐dependent oxidoreductase.

show abstract

Discovery of Novel Tyrosine Ammonia Lyases for the Enzymatic Synthesis of p‐Coumaric Acid

Brack

¹

,

Sun

²

,

Dong

³

et al. 2022

Self Cite

View full text Add to dashboard Cite

p-Coumaric acid (p-CA) is a key precursor for the biosynthesis of flavonoids. Tyrosine ammonia lyases (TALs) specifically catalyze the synthesis of p-CA from l-tyrosine, which is a convenient enzymatic pathway. To explore novel and highly active TALs, a phylogenetic tree-building approach was conducted including 875 putative TALs and 46 putative phenylalanine/tyrosine ammonia lyases (PTALs). Among them, 5 TALs and 3 PTALs were successfully characterized and found to exhibit the proposed enzymatic activity. The TAL from Chryseobacterium luteum sp. nov (TAL clu ) has the highest affinity (K m = 0.019 mm) and conversion efficiency (k cat /K m = 1631 s À 1 • mm À 1 ) towards ltyrosine. The reaction conditions for two purified enzymes and their E. coli recombinant cells were optimized and p-CA yields of 2.03 g/L after 8 hours by TAL clu and 2.35 g/L after 24 h by TAL from Rivularia sp. PCC 7116 (TAL rpc ) in whole cells were achieved. These TALs are thus candidates for the construction of whole-cell systems to produce the flavonoid precursor p-CA.

show abstract

Entdeckung neuer bakterieller Chalconisomerasen durch eine Sequenz‐Struktur‐Funktions‐Evolutions‐Strategie für die enzymatische Synthese von (S)‐Flavanonen

Cited by 3 publications

References 19 publications

Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining

Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining

Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining

Discovery of Novel Tyrosine Ammonia Lyases for the Enzymatic Synthesis of p‐Coumaric Acid

Contact Info

Product

Resources

About