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1.
Appl Microbiol Biotechnol ; 108(1): 409, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970663

ABSTRACT

Vitamin D deficiencies are linked to multiple human diseases. Optimizing its synthesis, physicochemical properties, and delivery systems while minimizing side effects is of clinical relevance and is of great medical and industrial interest. Biotechnological techniques may render new modified forms of vitamin D that may exhibit improved absorption, stability, or targeted physiological effects. Novel modified vitamin D derivatives hold promise for developing future therapeutic approaches and addressing specific health concerns related to vitamin D deficiency or impaired metabolism, such as avoiding hypercalcemic effects. Identifying and engineering key enzymes and biosynthetic pathways involved, as well as developing efficient cultures, are therefore of outmost importance and subject of intense research. Moreover, we elaborate on the critical role that microbial bioconversions might play in the a la carte design, synthesis, and production of novel, more efficient, and safer forms of vitamin D and its analogs. In summary, the novelty of this work resides in the detailed description of the physiological, medical, biochemical, and epidemiological aspects of vitamin D supplementation and the steps towards the enhanced and simplified industrial production of this family of bioactives relying on microbial enzymes. KEY POINTS: • Liver or kidney pathologies may hamper vitamin D biosynthesis • Actinomycetes are able to carry out 1α- or 25-hydroxylation on vitamin D precursors.


Subject(s)
Biotransformation , Vitamin D , Vitamin D/metabolism , Humans , Biosynthetic Pathways/genetics , Metabolic Engineering/methods , Actinobacteria/metabolism , Actinobacteria/genetics , Biotechnology/methods , Bacteria/metabolism , Bacteria/genetics , Hydroxylation
2.
J Phycol ; 59(2): 356-369, 2023 04.
Article in English | MEDLINE | ID: mdl-36690599

ABSTRACT

Dunaliella tertiolecta RCC6 was cultivated indoors in glass bubble column photobioreactors operated under batch and semi-continuous regimens and using two different conditions of light and temperature. Biomass was harvested by centrifugation, frozen, and then lyophilized. The soluble material was obtained by sequential extraction of the lyophilized biomass with solvents with a gradient of polarity (hexane, ethyl acetate, and methanol) and its metabolic composition was investigated through nuclear magnetic resonance (NMR) spectroscopy. The effect of light on chlorophyll biosynthesis was clearly shown through the relative intensities of the 1 H NMR signals due to pheophytins. The highest signal intensity was observed for the biomasses obtained at lower light intensity, resulting in a lower light availability per cell. Under high temperature and light conditions, the 1 H NMR spectra of the hexane extracts showed an incipient accumulation of triacylglycerols. In these conditions and under semi-continuous regimen, an enhancement of ß-carotene and sterols production was observed. The antibacterial and antibiofilm activities of the extracts were also tested. Antibacterial activity was not detected, regardless of culture conditions. In contrast, the minimal biofilm inhibitory concentrations (MBICs) against Escherichia coli for the hexane extract obtained under semi-continuous regimen using high temperature and irradiance conditions was promising.


Subject(s)
Chlorophyceae , Hexanes , Anti-Bacterial Agents/pharmacology , Biofilms
3.
Mar Drugs ; 19(12)2021 Nov 27.
Article in English | MEDLINE | ID: mdl-34940674

ABSTRACT

Lipids are one of the primary metabolites of microalgae and cyanobacteria, which enrich their utility in the pharmaceutical, feed, cosmetic, and chemistry sectors. This work describes the isolation, structural elucidation, and the antibiotic and antibiofilm activities of diverse lipids produced by different microalgae and cyanobacteria strains from two European collections (ACOI and LEGE-CC). Three microalgae strains and one cyanobacteria strain were selected for their antibacterial and/or antibiofilm activity after the screening of about 600 strains carried out under the NoMorFilm European project. The total organic extracts were firstly fractionated using solid phase extraction methods, and the minimum inhibitory concentration and minimal biofilm inhibitory concentration against an array of human pathogens were determined. The isolation was carried out by bioassay-guided HPLC-DAD purification, and the structure of the isolated molecules responsible for the observed activities was determined by HPLC-HRESIMS and NMR methods. Sulfoquinovosyldiacylglycerol, monogalactosylmonoacylglycerol, sulfoquinovosylmonoacylglycerol, α-linolenic acid, hexadeca-4,7,10,13-tetraenoic acid (HDTA), palmitoleic acid, and lysophosphatidylcholine were found among the different active sub-fractions selected. In conclusion, cyanobacteria and microalgae produce a great variety of lipids with antibiotic and antibiofilm activity against the most important pathogens causing severe infections in humans. The use of these lipids in clinical treatments alone or in combination with antibiotics may provide an alternative to the current treatments.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Cyanobacteria , Lipids/pharmacology , Microalgae , Animals , Anti-Bacterial Agents/chemistry , Aquatic Organisms , Lipids/chemistry , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects
4.
Int J Mol Sci ; 22(18)2021 Sep 20.
Article in English | MEDLINE | ID: mdl-34576306

ABSTRACT

Streptomycetes are important biotechnological bacteria that produce several clinically bioactive compounds. They have a complex development, including hyphae differentiation and sporulation. Cytosolic copper is a well-known modulator of differentiation and secondary metabolism. The interruption of the Streptomyces coelicolor SCO2730 (copper chaperone, SCO2730::Tn5062 mutant) blocks SCO2730 and reduces SCO2731 (P-type ATPase copper export) expressions, decreasing copper export and increasing cytosolic copper. This mutation triggers the expression of 13 secondary metabolite clusters, including cryptic pathways, during the whole developmental cycle, skipping the vegetative, non-productive stage. As a proof of concept, here, we tested whether the knockdown of the SCO2730/31 orthologue expression can enhance secondary metabolism in streptomycetes. We created a SCO2730/31 consensus antisense mRNA from the sequences of seven key streptomycetes, which helped to increase the cytosolic copper in S. coelicolor, albeit to a lower level than in the SCO2730::Tn5062 mutant. This antisense mRNA affected the production of at least six secondary metabolites (CDA, 2-methylisoborneol, undecylprodigiosin, tetrahydroxynaphtalene, α-actinorhodin, ε-actinorhodin) in the S. coelicolor, and five (phenanthroviridin, alkylresorcinol, chloramphenicol, pikromycin, jadomycin G) in the S. venezuelae; it also helped to alter the S. albus metabolome. The SCO2730/31 consensus antisense mRNA designed here constitutes a tool for the knockdown of SCO2730/31 expression and for the enhancement of Streptomyces' secondary metabolism.


Subject(s)
Bacterial Proteins/metabolism , Copper-Transporting ATPases/metabolism , Molecular Chaperones/metabolism , Secondary Metabolism , Streptomyces coelicolor/metabolism , Bacterial Proteins/genetics , Copper/metabolism , Copper-Transporting ATPases/genetics , Molecular Chaperones/genetics , Streptomyces coelicolor/genetics
5.
J Nat Prod ; 83(6): 1885-1890, 2020 06 26.
Article in English | MEDLINE | ID: mdl-32479093

ABSTRACT

Four natural lactylates of chlorinated fatty acids, chlorosphaerolactylates A-D (1-4), were isolated from the methanolic extract of the cyanobacterium Sphaerospermopsis sp. LEGE 00249 through a combination of bioassay-guided and MS-guided approaches. Compounds 1-4 are esters of (mono-, di-, or tri)chlorinated lauric acid and lactic acid, whose structures were assigned on the basis of spectrometric and spectroscopic methods inclusive of 1D and 2D NMR experiments. High-resolution mass-spectrometry data sets also demonstrated the existence of other minor components that were identified as chlorosphaero(bis)lactylate analogues. The chlorosphaerolactylates were tested for potential antibacterial, antifungal, and antibiofilm properties using bacterial and fungal clinical isolates. Compounds 1-4 showed a weak inhibitory effect on the growth of Staphylococcus aureus S54F9 and Candida parapsilosis SMI416, as well as on the biofilm formation of coagulase-negative Staphylococcus hominis FI31.


Subject(s)
Anti-Infective Agents/chemistry , Cyanobacteria/chemistry , Fatty Acids/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Antifungal Agents/pharmacology , Biofilms/drug effects , Candida/drug effects , Fatty Acids/isolation & purification , Fatty Acids/pharmacology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Molecular Structure , Staphylococcus aureus/drug effects , Staphylococcus hominis/drug effects
6.
Front Microbiol ; 13: 950855, 2022.
Article in English | MEDLINE | ID: mdl-36246241

ABSTRACT

Chlorosphaerolactylate B, a newly discovered antimicrobial halometabolite from the cyanobacterium Sphaerospermopsis sp. LEGE 00249 has been synthesized in three steps by using 12-bromododecanoic acid as starting material. A total of 0.5 g was produced for in vitro and in vivo antimicrobial efficacy testing. In vitro, the minimal inhibitory concentration (MIC) was estimated to be 256 mg/L for Staphylococcus aureus, while the minimal biofilm inhibitory concentration (MBIC) was estimated to be 74 mg/L. The in vivo study utilized a porcine model of implant-associated osteomyelitis. In total, 12 female pigs were allocated into 3 groups based on inoculum (n = 4 in each group). An implant cavity (IC) was drilled in the right tibia and followed by inoculation and insertion of a steel implant. All pigs were inoculated with 10 µL containing either: 11.79 mg synthetic Chlorosphaerolactylate B + 104 CFU of S. aureus (Group A), 104 CFU of S. aureus (Group B), or pure saline (Group C), respectively. Pigs were euthanized five days after inoculation. All Group B animals showed macroscopic and microscopic signs of bone infection and both tissue and implant harbored S. aureus bacteria (mean CFU on implants = 1.9 × 105). In contrast, S. aureus could not be isolated from animals inoculated with saline. In Group A, two animals had a low number of S. aureus (CFU = 6.7 × 101 and 3.8 × 101, respectively) on the implants, otherwise all Group A animals were similar to Group C animals. In conclusion, synthetic Chlorosphaerolactylate B holds potential to be a novel antimicrobial and antibiofilm compound.

7.
Microb Biotechnol ; 14(5): 2009-2024, 2021 09.
Article in English | MEDLINE | ID: mdl-34216097

ABSTRACT

Flavonoids are important plant secondary metabolites, which were shown to have antioxidant, anti-inflammatory or antiviral activities. Heterologous production of flavonoids in engineered microbial cell factories is an interesting alternative to their purification from plant material representing the natural source. The use of engineered bacteria allows to produce specific compounds, independent of soil, climatic or other plant-associated production parameters. The initial objective of this study was to achieve an engineered production of two interesting flavanonols, garbanzol and fustin, using Streptomyces albus as the production host. Unexpectedly, the engineered strain produced several flavones and flavonols in the absence of the additional expression of a flavone synthase (FNS) or flavonol synthase (FLS) gene. It turned out that the heterologous flavanone 3-hydroxylase (F3H) has a 2-hydroxylase side activity, which explains the observed production of 7,4'-dihydroxyflavone, resokaempferol, kaempferol and apigenin, as well as the biosynthesis of the extremely rare 2-hydroxylated intermediates 2-hydroxyliquiritigenin, 2-hydroxynaringenin and probably licodione. Other related metabolites, such as quercetin, dihydroquercetin and eriodictyol, have also been detected in culture extracts of this recombinant strain. Hence, the enzymatic versatility of S. albus can be conveniently exploited for the heterologous production of a large diversity of plant metabolites of the flavonoid family.


Subject(s)
Flavonoids , Mixed Function Oxygenases , Mixed Function Oxygenases/genetics , Streptomyces
8.
Antioxidants (Basel) ; 10(8)2021 Aug 08.
Article in English | MEDLINE | ID: mdl-34439512

ABSTRACT

Synthetic antioxidant food additives, such as BHA, BHT and TBHQ, are going through a difficult time, since these products generate a negative perception in consumers. This has generated an increased pressure on food manufacturers to search for safer natural alternatives like phytochemicals (such as polyphenols, including flavonoids, and essential oils rich in terpenoids, including carotenoids). These plant bioactive compounds have antioxidant activities widely proven in in vitro tests and in diverse food matrices (meat, fish, oil and vegetables). As tons of food are wasted every year due to aesthetic reasons (lipid oxidation) and premature damage caused by inappropriate packaging, there is an urgent need for natural antioxidants capable of replacing the synthetic ones to meet consumer demands. This review summarizes industrially interesting antioxidant bioactivities associated with terpenoids and polyphenols with respect to the prevention of lipid oxidation in high fat containing foods, such as meat (rich in saturated fat), fish (rich in polyunsaturated fat), oil and vegetable products, while avoiding the generation of rancid flavors and negative visual deterioration (such as color changes due to oxidized lipids). Terpenoids (like monoterpenes and carotenoids) and polyphenols (like quercetin and other flavonoids) are important phytochemicals with a broad range of antioxidant effects. These phytochemicals are widely distributed in fruits and vegetables, including agricultural waste, and are remarkably useful in food preservation, as they show bioactivity as plant antioxidants, able to scavenge reactive oxygen and nitrogen species, such as superoxide, hydroxyl or peroxyl radicals in meat and other products, contributing to the prevention of lipid oxidation processes in food matrices.

9.
Nanomaterials (Basel) ; 11(4)2021 Apr 20.
Article in English | MEDLINE | ID: mdl-33924070

ABSTRACT

In our study, we demonstrated the performance of antimicrobial coatings on properly functionalized and nanostructured 316L food-grade stainless steel pipelines. For the fabrication of these functional coatings, we employed facile and low-cost electrochemical techniques and surface modification processes. The development of a nanoporous structure on the 316L stainless steel surface was performed by following an electropolishing process in an electrolytic bath, at a constant anodic voltage of 40 V for 10 min, while the temperature was maintained between 0 and 10 °C. Subsequently, we incorporated on this nanostructure additional coatings with antimicrobial and bactericide properties, such as Ag nanoparticles, Ag films, or TiO2 thin layers. These functional coatings were grown on the nanostructured substrate by following electroless process, electrochemical deposition, and atomic layer deposition (ALD) techniques. Then, we analyzed the antimicrobial efficiency of these functionalized materials against different biofilms types (Candida parapsilosis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis). The results of the present study demonstrate that the nanostructuring and surface functionalization processes constitute a promising route to fabricate novel functional materials exhibiting highly efficient antimicrobial features. In fact, we have shown that our use of an appropriated association of TiO2 layer and Ag nanoparticle coatings over the nanostructured 316L stainless steel exhibited an excellent antimicrobial behavior for all biofilms examined.

10.
Phytochemistry ; 164: 192-205, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31174083

ABSTRACT

The chemical composition of five marine microalgae (Dunaliella sp., Dunaliella salina, Chaetoceros calcitrans, Chaetoceros gracilis and Tisochrysis lutea) was investigated through nuclear magnetic resonance (NMR) spectroscopic study of the soluble material obtained by sequential extraction with hexane, ethyl acetate (AcOEt) and methanol of biomass from stationary phase cultures. Hexane extracted the major lipids present in the microalgae during the stationary phase of growth, which correspond to storage lipids. Triacylglycerols (TGs) were the only storage lipids produced by Dunaliella and Chaetoceros. In contrast, T. lutea predominantly stored polyunsaturated long-chain alkenones, with sterols also detected as minor components of the hexane extract. The molecular structure of brassicasterol was determined in T. lutea and the presence of squalene in this sample was also unequivocally detected. Monogalactosyldiacylglycerols (MGDGs) and pigments were concentrated in the AcOEt extracts. C. calcitrans and D. salina constituted an exception due to the high amount of TGs and glycerol produced, respectively, by these two strains. Chlorophylls a and b and ß-carotene were the major pigments synthesized by Dunaliella and chlorophyll a and fucoxanthin were the only pigments detected in Chaetoceros and T. lutea. Information concerning the acyl chains present in TGs and MGDGs as well as the positional distribution of acyl chains on the glycerol moiety was obtained by NMR analysis of hexane and AcOEt extracts, with results consistent with those expected for the genera studied. Fatty acid composition of TGs in the two Dunaliella strains was different, with polyunsaturated acyl chains almost absent in the storage lipids produced by D. salina. Except in C. calcitrans, the polar nature of soluble compounds was inferred through the relative extraction yield using methanol as the extraction solvent. Glycerol was the major component of this fraction for the Dunaliella strains. In T. lutea 1,4/2,5-cyclohexanetetrol (CHT) and dimethylsulfoniopropionate (DMSP) preponderated. CHT was also the major polyol present in the Chaetoceros strains in which DMSP was not detected, but prominent signals of 2,3-dihydroxypropane-1-sulfonate (DHSP) were observed in the 1H NMR spectra of methanolic extracts. The presence of DHSP confirms the production of this metabolite by diatoms. In addition, several other minor compounds (digalactosyldiacyglycerols (DGDGs), sulphoquinovosyldiacylglycerols (SQDGs), amino acids, carbohydrates, scyllo-inositol, mannitol, lactic acid and homarine) were also identified in the methanolic extracts. The antibacterial and antibiofilm activities of the extracts were tested. The AcOEt extract from C. gracilis showed a moderate antibiofilm activity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Biofilms/drug effects , Microalgae/chemistry , Nuclear Magnetic Resonance, Biomolecular , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microalgae/metabolism , Microbial Sensitivity Tests , Molecular Conformation
11.
Int J Antimicrob Agents ; 52(3): 309-315, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29777759

ABSTRACT

Synthetic food additives generate a negative perception in consumers. Therefore, food manufacturers search for safer natural alternatives such as those involving phytochemicals and plant essential oils. These bioactive compounds have antimicrobial activities widely proven in in vitro tests. Foodborne diseases cause thousands of deaths and millions of infections every year, mainly due to pathogenic bacteria such as Salmonella spp., Campylobacter spp., Escherichia coli, Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus. This review summarises industrially interesting antimicrobial bioactivities as well as their mechanisms of action for three main types of plant nutraceuticals, namely terpenoids (e.g. carnosic acid), polyphenols (e.g. quercetin) and thiols (e.g. allicin), which are important constituents of plant essential oils with a broad range of antimicrobial effects. These phytochemicals are widely distributed in fruits and vegetables and are especially useful in food preservation as microbial growth inhibitors.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/growth & development , Food Preservation/methods , Food Preservatives/pharmacology , Foodborne Diseases/prevention & control , Oils, Volatile/pharmacology , Phytochemicals/pharmacology , Plant Oils/pharmacology , Bacteria/drug effects , Dietary Supplements , Food Microbiology , Humans , Microbial Sensitivity Tests , Polyphenols/pharmacology , Terpenes/pharmacology
12.
PLoS One ; 13(11): e0207278, 2018.
Article in English | MEDLINE | ID: mdl-30440014

ABSTRACT

Flavonols are a flavonoid subfamily widely distributed in plants, including several ones of great importance in human and animal diet (apple, tomato, broccoli, onion, beans, tea). These polyphenolic nutraceuticals exert potent antimicrobial (membrane potential disruptors), antioxidant (free-radical scavengers), pharmacokinetic (CYP450 modulators), anti-inflammatory (lipoxygenase inhibitors), antiangiogenic (VEGF inhibitors) and antitumor (cyclin inhibitors) activities. Biotechnological production of these nutraceuticals, for example via heterologous biosynthesis in industrial actinomycetes, is favored since in plants these polyphenols appear as inactive glycosylated derivatives, in low concentrations or as part of complex mixtures with other polyphenolic compounds. In this work, we describe the de novo biosynthesis of three important flavonols, myricetin, kaempferol and quercetin, in the industrially relevant actinomycetes Streptomyces coelicolor and S. albus. De novo biosynthesis of kaempferol, myricetin and quercetin in actinomycetes has not been described before.


Subject(s)
Dietary Supplements , Flavonoids , Kaempferols , Microorganisms, Genetically-Modified , Quercetin , Streptomyces coelicolor , Flavonoids/biosynthesis , Flavonoids/genetics , Kaempferols/biosynthesis , Kaempferols/genetics , Microorganisms, Genetically-Modified/genetics , Microorganisms, Genetically-Modified/metabolism , Quercetin/biosynthesis , Quercetin/genetics , Streptomyces coelicolor/genetics , Streptomyces coelicolor/metabolism
13.
PLoS One ; 13(1): e0184277, 2018.
Article in English | MEDLINE | ID: mdl-29304041

ABSTRACT

Drinking water can be exposed to different biological contaminants from the source, through the pipelines, until reaching the final consumer or industry. Some of these are pathogenic bacteria and viruses which may cause important gastrointestinal or systemic diseases. The microbiological quality of drinking water relies mainly in monitoring three indicator bacteria of faecal origin, Escherichia coli, Enterococcus faecalis and Clostridium perfringens, which serve as early sentinels of potential health hazards for the population. Here we describe the analysis of three chimeric fluorescent protein bullets as biosensor candidates for fast detection of E. coli in drinking water. Two of the chimeric proteins (based on GFP-hadrurin and GFP-pb5 chimera proteins) failed with respect to specificity and/or sensitivity, but the GFP-colS4 chimera protein was able to carry out specific detection of E. coli in drinking water samples in a procedure encompassing about 8 min for final result and this biosensor protein was able to detect in a linear way between 20 and 103 CFU of this bacterium. Below 20 CFU, the system cannot differentiate presence or absence of the target bacterium. The fluorescence in this biosensor system is provided by the GFP subunit of the chimeric protein, which, in the case of the better performing sensor bullet, GFP-colS4 chimera, is covalently bound to a flexible peptide bridge and to a bacteriocin binding specifically to E. coli cells. Once bound to the target bacteria, the excitation step with 395 nm LED light causes emission of fluorescence from the GFP domain, which is amplified in a photomultiplier tube, and finally this signal is converted into an output voltage which can be associated with a CFU value and these data distributed along mobile phone networks, for example. This method, and the portable fluorimeter which has been developed for it, may contribute to reduce the analysis time for detecting E. coli presence in drinking water.


Subject(s)
Biosensing Techniques/methods , Drinking Water/microbiology , Escherichia coli/isolation & purification , Water Microbiology , Bacterial Load/methods , Bacterial Load/statistics & numerical data , Colicins/chemistry , Colicins/genetics , Escherichia coli/genetics , Fluorometry/instrumentation , Green Fluorescent Proteins/chemistry , Green Fluorescent Proteins/genetics , Humans , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics
14.
Front Pharmacol ; 8: 109, 2017.
Article in English | MEDLINE | ID: mdl-28352231

ABSTRACT

Combination therapy consists in the simultaneous administration of a conventional chemotherapy drug (or sometimes, a radiotherapy protocol) together with one or more natural bioactives (usually from plant or fungal origin) of small molecular weight. This combination of anticancer drugs may be applied to cell cultures of tumor cells, or to an animal model for a cancer type (or its xenograft), or to a clinical trial in patients. In this review, we summarize current knowledge describing diverse synergistic effects on colorectal cancer cell cultures, animal models, and clinical trials of various natural bioactives (stilbenes, flavonoids, terpenes, curcumin, and other structural families), which may be important with respect to diminish final doses of the chemotherapy drug, although maintaining its biological effect. This is important as these approaches may help reduce side effects in patients under conventional chemotherapy. Also, these molecules may exerts their synergistic effects via different cell cycle pathways, including different ones to those responsible of resistance phenotypes: transcription factors, membrane receptors, adhesion and structural molecules, cell cycle regulatory components, and apoptosis pathways.

15.
Front Microbiol ; 8: 921, 2017.
Article in English | MEDLINE | ID: mdl-28611737

ABSTRACT

Nutraceutical compounds as plant flavonoids play an important role in prevention and modulation of diverse heath conditions, as they exert interesting antifungal, antibacterial, antioxidant, and antitumor effects. They also possess anti-inflammatory activities in arthritis, cardiovascular disease or neurological diseases, as well as modulatory effects on the CYP450 activity on diverse drugs. Most flavonoids are bioactive molecules of plant origin, but their industrial production is sometimes hindered due to reasons as low concentration in the plant tissues, presence in only some species or as a complex mixture or inactive glycosides in plant vacuolae. In this work, we describe the de novo biosynthesis of two important flavones, apigenin and luteolin, and one known flavanone, eriodictyol. Their plant biosynthetic pathways have been reconstructed for heterologous expression in Streptomyces albus, an actinomycete bacterium manageable at industrial production level. Also, production levels for apigenin have been improved by feeding with naringenin precursor, and timing for settlement of secondary metabolism has been advanced by spore conditioning. In the cases of eriodictyol and luteolin, their production in this important type of biotechnology-prone bacteria, the actinomycetes, had not been described in the literature yet.

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