Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi, but also prevents the formation of some mycotoxins. Consequently, it has been approved for use as an antifungal food preservative in most countries, and is also widely used in agriculture and healthcare. Streptomyces natalensis and Streptomyces chatanoogensis are the main producers of natamycin. This review summarizes the biosynthesis and regulatory mechanism of natamycin, as well as the strategies for improving natamycin production. Moreover, the future perspectives on natamycin research are discussed.
Antifungal Agents/pharmacology* ; Fungi ; Natamycin ; Streptomyces

We isolated a high efficient antifungal strain A02 from forest soil in a suburb of Beijing. The result of polyphasic taxonomy confirmed that strain A02 belongs to Streptomyces lydicus. The fermented broth of the strain presented a stable and strong inhibiting activity against many plant pathogenic fungi. The purpose of this study was to ascertain the substance base of the antifungal activity of strain A02. We extracted the antifungal metabolite of A02 by using column chromatography with X-5 macroporous resin and 100-200 mesh silica gel respectively, and then purified it by LC-9101 recycling preparative HPLC with a SP-120-15 column (JAIGEL-ODS-AP). An active compound with purity over 99.845% was finally obtained. The chemical structure of the active compound was determined with spectroscopy methods, including ultraviolet spectrometry, infrared spectrometry, high resolution mass spectrometry and nuclear magnetic resonance. According to the analysis results, we identified the active compound as a tetraene macrolide antibiotic with the molecular weight of 665, the molecular formula C33H47No3 and the same chemical structure as natamycin. Our research revealed a new biosynthetic function for S. lydicus to produce natamycin, and an expanding application field for natamycin to be used for the control of fungal plant diseases.
Antifungal Agents ; chemistry ; isolation & purification ; Natamycin ; analogs & derivatives ; Soil Microbiology ; Streptomyces ; chemistry ; isolation & purification ; metabolism

The afsRS(cla) global regulatory genes from Streptomyces clavuligerus activate the production of two antibiotics in Streptomyces lividans. In this study, we gained an increase of 38% in the production of natamycin (3.56 g/L) in an industrial strain Streptomyces gilvosporeus TZ1401 through the integration of pHL851 that bears the afsRS(cla) global regulatory genes into its genome. We discovered by quantitive real-time reverse transcription PCR (qRT-PCR) that the expression of 6 genes of the natamycin biosynthetic gene cluster were improved from 1.9 to 2.7 times. This suggests that afsRS(cla) improve the production of natamycin through increased transcription. This study provides a good example for applying afsRS(cla) in high yield breeding of industrial antibiotic producers.
Anti-Bacterial Agents ; biosynthesis ; Genes, Regulator ; Industrial Microbiology ; Multigene Family ; Natamycin ; biosynthesis ; Streptomyces ; genetics

PURPOSE: To report a case of fungal keratitis caused by Drechslera species. CASE SUMMARY: A 77-year-old man visited our clinic complaining of left ocular pain and decrease of visual acuity for 1 week On slit-lamp examination, epithelial defect and stromal infiltration on the corneal center with numerous inflammatory cells in the anterior chamber were found. There was no improvement after routine antibiotic treatment. A corneal biopsy and culture were performed on the corneal lesion. The KOH smear study reported hyphae, thus the patient was treated with 0.25% amphotericin B, 0.2% fluconazole and 5% natamycin eye drops. A clinical improvement was observed on the corneal lesion and Drechslera species was identified by the culture study. CONCLUSIONS: The authors report an experience of fungal keratitis caused by Drechslera species.
Aged ; Amphotericin B ; Anterior Chamber ; Biopsy ; Fluconazole ; Humans ; Hyphae ; Keratitis ; Natamycin ; Ophthalmic Solutions ; Visual Acuity

PURPOSE: To present a case report of fungal keratitis related to prolonged overnight use of orthokeratology contact lenses. METHODS: A 13 year-old girl presented with a corneal ulcer in her left eye refractory to antibacterial medication. She had a history of wearing orthokeratology contact lenses overnight for seven months. RESULTS: The organism Aspergillus was isolated by corneal scraping, the contact lens itself, and from the storage case. The patient was treated with topical fluconazole and Natamycin pimaricin in addition to oral itraconazole, resulting in a resolution of the ocular lesion. CONCLUSIONS: The risk of fungal infection as a potential complication of the use of overnight orthkeratology contact lenses should be considered when using these lenses.
Adolescent ; Aspergillus ; Contact Lenses ; Corneal Ulcer ; Female ; Fluconazole ; Humans ; Itraconazole ; Keratitis* ; Natamycin

Fungal corneal ulcer could lead to a devastating outcome. The relative scarcity of readily available, inexpensive but effective topical antifungal drug has left many ophthalmologists desperate and frustated in treating the condition. The use of oral itraconazole has long been proven to be of clinical value in a number of forms of mycoses. Its safety profile is extremely good with minimal reported adverse effects. We investigated an aqueous form of itraconazole which we prepared into a 0.1 mg/ml concnetration and compared its efficacy as a topical antifungal against the standard drug. Natamycin 5 percent in the treatment of fungal keratitis in rabbits. A randomized animal trial was done using 24 rabbit eyes divided into 2 treatment groups. All rabbit corneas were inoculated with Aspergillus flavus and treated after 48 hours with either Topical itraconazole or Natamycin 5 percent for a period of 2 weeks. Results showed inhibition of the disease with both treatment groups. We also found no significant difference between the severity, progression and remission of the keratitis between both treatment groups clinically and statistically. Topical itraconazole 0.1 mg/ml was shown to be comparable to our standard topical antifungal Natamycin 5 percent in treating fungal keratitis. (Author)
Animal ; ASPERGILLUS KERATITIS ; OPHTHALMOLOGY ; ASPERGILLUS FLAVUS ; NATAMYCIN ; ITRACONAZOLE ; FUNGAL CORNEAL ULCER ; FUNGAL KERATITIS

Natamycin is a safe and efficient antimycotics which is widely used in food and medicine industry. The polyene macrolide compound, produced by several bacterial species of the genus Streptomyces, is synthesized by type Ⅰ polyketide synthases using acetyl-CoA, malonyl-CoA, and methylmalonyl-CoA as substrates. In this study, four pathways potentially responsible for the supply of the three precursors were evaluated to identify the effective precursor supply pathway which can support the overproduction of natamycin in Streptomyces gilvosporeus, a natamycin-producing wild-type strain. The results showed that over-expressing acetyl-CoA synthetase and methylmalonyl-CoA mutase increased the yield of natamycin by 44.19% and 20.51%, respectively, compared with the wild type strain under shake flask fermentation. Moreover, the yield of natamycin was increased by 66.29% compared with the wild-type strain by co-overexpression of acetyl-CoA synthetase and methylmalonyl-CoA mutase. The above findings will facilitate natamycin strain improvement as well as development of strains for producing other polyketide compounds.
Natamycin/metabolism* ; Methylmalonyl-CoA Mutase/metabolism* ; Acetyl Coenzyme A/metabolism* ; Streptomyces/genetics* ; Polyketide Synthases/metabolism*

PURPOSE: To present a case report of fungal keratitis related to prolonged overnight use of orthokeratology contact lenses. METHODS: A 13 year-old girl presented with a corneal ulcer in her left eye refractory to antibacterial medication. She had a history of wearing orthokeratology contact lenses overnight for seven months. RESULTS: The organism Aspergillus was isolated by corneal scraping, the contact lens itself, and from the storage case. The patient was treated with topical fluconazole and Natamycin pimaricin in addition to oral itraconazole, resulting in a resolution of the ocular lesion. CONCLUSIONS: The risk of fungal infection as a potential complication of the use of overnight orthkeratology contact lenses should be considered when using these lenses.
Aspergillus ; Contact Lenses ; Corneal Dystrophies, Hereditary ; Corneal Ulcer ; Eye ; Fluconazole ; Humans ; Itraconazole ; Keratitis ; Keratomileusis, Laser In Situ ; Natamycin

PURPOSE: Chromomycetes is a plant parasite and one of the pigmented filamentous fungi, which rarely causes human infection. The authors report the first case of fungal keratitis caused by chromomycetes in korea. METHODS: A 65-year-old woman developed pain, redness, and an yellowish-brown infiltrate in her right eye. She had a history of corneal scratch by a pumpkin stalk and transferred by a local clinic after management for about 1 months. The clinical features suggested fungal keratitis, and the patient was undertaken surgical debridement with amniotic membrane graft and treated with oral terbinafine with natamycin and amphotericin B eyedrops. Surgically taken biopsy specimen was cultured. Amniotic membrane was removed after 1 week. After slight improvement of symptom, necrotizing ulceration was enlarged in spite of continuous antifungal therapy. Lamellar keratoplasty with amniotic membrane graft was done with antifungal therapy. Systemic agent was changed to fluconazole. Clinical improvement was achieved after about 2 months. The fungus was identified as Fonsecaea pedrosoi. RESULTS: Fungal keratitis was successfully treated with antifungal medication combined with amniotic membrane graft. CONCLUSIONS: This is a rare case of infectious keratitis caused by chromomycetes. But its clinical course was severe, so exact culture and identification following aggressive surgical and medical treatment was needed.
Aged ; Amnion ; Amphotericin B ; Biopsy ; Chromoblastomycosis ; Corneal Transplantation ; Corneal Ulcer ; Cucurbita ; Debridement ; Female ; Fluconazole ; Fungi ; Humans ; Keratitis* ; Korea ; Natamycin ; Ophthalmic Solutions ; Parasites ; Plants ; Transplants ; Ulcer

Though topical administration of antifungal agents for fungal keratitis is effective, it results various toxic effect on cornea depending on the kinds of agents. So, the authors applied several kinds of antifungal agents on the cornea of rabbit and made a comparative study for corneal epithelial damage of which is related to each agents and instillation time using scanning electron microscope. Forty eyes from twenty rabbits were instilled with 0.15% amphotericin B, 5% natamycin, 1% clotrimazole, 0.2% fluconazole and BSS(as a control) in single drop in each eight eyes and then each two corneas resected and examined after 30 minutes, 1 hours, 3 hours and 6 hours. All antifungals showed toxic effects on the corneal epithelium. Significant loss, elongation or swelling in microvilli, especially at the cell periphery, were noted. The top layer of epithelial cells showed moth-eaten appearance or punched-out lesions, and localized destruction. The surface cells were shrunken with wrinkling of plasma membrane and bulging of nucleous. Part of surface cells lost intercellular attachment leaving retraction fibrils. Rarely first and second layer cells of the epithelium were destructed, exposing third layer cells. Dark cells and premature desquamating cells increased significantly with the lapse of time. In general, 5% natamycin and 1% clotrimazole showed relatively severe epithelial toxicity, on the other hand, 0.15% amphotericin B and 0.2% fluconazole shoed mild epithelial toxicity. Localized damages in the epithelial cells were developed in the early stage, and an extent and the depth of the damage in the cells increased in the course of time after instillation.
Administration, Topical ; Amphotericin B ; Antifungal Agents* ; Cell Membrane ; Clotrimazole ; Cornea ; Epithelial Cells ; Epithelium ; Epithelium, Corneal* ; Fluconazole ; Hand ; Keratitis ; Microscopy, Electron, Scanning ; Microvilli ; Natamycin ; Rabbits*