Molecular genetics of naringenin biosynthesis, a typical plant secondary metabolite produced by Streptomyces clavuligerus

Abstract

BackgroundSome types of flavonoid intermediates seemed to be restricted to plants. Naringenin is a typical plant metabolite, that has never been reported to be produced in prokariotes. Naringenin is formed by the action of a chalcone synthase using as starter 4-coumaroyl-CoA, which in dicotyledonous plants derives from phenylalanine by the action of a phenylalanine ammonia lyase.ResultsA compound produced by Streptomyces clavuligerus has been identified by LC–MS and NMR as naringenin and coelutes in HPLC with a naringenin standard. Genome mining of S. clavuligerus revealed the presence of a gene for a chalcone synthase (ncs), side by side to a gene encoding a P450 cytochrome (ncyP) and separated from a gene encoding a Pal/Tal ammonia lyase (tal). Deletion of any of these genes results in naringenin non producer mutants. Complementation with the deleted gene restores naringenin production in the transformants. Furthermore, naringenin production increases in cultures supplemented with phenylalanine or tyrosine.ConclusionThis is the first time that naringenin is reported to be produced naturally in a prokariote. Interestingly three non-clustered genes are involved in naringenin production, which is unusual for secondary metabolites. A tentative pathway for naringenin biosynthesis has been proposed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-015-0373-7) contains supplementary material, which is available to authorized users.

Unique secondary metabolites of a Streptomyces strain isolated from extreme salty wetland show antioxidant and antibacterial activities

“…As expected, most of the compounds identified in the chemical analysis were reported before as secondary metabolites of Streptomyces , such as naringenin, the aglycone of narirutin (Álvarez‐Álvarez et al ), γ ‐actinorhodin (Nass et al ), germicidins (Čihák et al ), geldanamycin (Fukuyo et al ), doxorubicin (Arcamone et al ), 4,5‐dihydrogeldanamycin (Lin et al ), albaflavenone (Lin and Cane ; Čihák et al ), lasalocid (Shichijo et al ), antimycin B2 (Han et al ), linearolide A (Ueki et al ) and ascomycin (Griffiths ). Interestingly, to our knowledge, genistein‐7‐ O ‐glucuronide, phenyl acetic acid, 7,3’,4’‐trihydroxyflavanone, resveratrol and mycophenolic acid have never been reported before in Streptomyces .…”

“…Resveratrol is linked to the beneficial effects of red wine and was associated with numerous food‐related biological activities including chelation of heavy metals, inhibition of lipid peroxidation (LDL, membranes), scavenging of free radical, anticancer and anti‐inflammatory properties, among others (Frémont ). The presence of secondary metabolites that are common in plants and bacteria has been reported in Streptomyces clavuligerus ATCC 27064 for the flavonoid naringenin (Álvarez‐Álvarez et al ).…”

“…4.0. The tentative identification of phenolics was carried out considering their UV and mass spectra, as well as by comparison of their retention time and fragmentation pattern with those of authentic standards when available and/or literature data (Braña et al ; Upadhyay et al ; Álvarez‐Álvarez et al ).…”

“…A general consensus emerged from these studies that extreme environments could represent an exceptional ecological niche for the discovery of novel Streptomyces species with an amazing assortment of useful compounds. The secondary metabolism of Streptomyces has been shown to be extremely rich in the production of many different chemicals, some of them common to phytochemicals (Álvarez‐Álvarez et al ), and also with a wide variety of bioactivities (Rani et al ). This threw light on our interest in these organisms and their secondary metabolites putting into consideration the number of emerging antibiotic‐resistant strains that is constantly increasing and the potential applications of secondary metabolites in medicine, food industry, cosmetics and environment (Zaidi et al ).…”

Verification of the phenylpropanoid pinoresinol biosynthetic pathway and its glycosides in Phomopsis sp. XP-8 using 13C stable isotope labeling and liquid chromatography coupled with time-of-flight mass spectrometry

“…Genomic annotation is an efficient way to discover the pathways that are normally difficult to reveal by metabolic and enzymatic evidence due to low intermediate accumulation, low end-product production, and silent gene expression under normal conditions. This method has been successfully used to identify the existence of a phenylpropanoid metabolic pathway in Aspergillus oryzae (28), and the molecular genetics of naringenin biosynthesis, a typical plant secondary metabolite in Streptomyces clavuligerus (29), and the occurrence of the phenylpropanoid-lignan pathway in Phomopsis sp. XP-8 (17).…”