Antifungal and antibacterial peptides, polypeptides and proteins as antifungal additives for paint and other coatings are disclosed, along with antifungal compositions, and coated surfaces with antifungal properties. Methods of using the coatings for treating and/or inhibiting growth of mold, mildew and other fungi and bacteria on objects such as building materials that are susceptible to such infestation are also disclosed.

Antifungal Paints and Coatings

INTRODUCTION .... . . . . . . .. . . . . . . . . . . . . . . . . . .. . . .... ... . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . .. . . . ... . . . . . . 271 HISTOR y . . . . . . ... . . ..... . . . . . . . . . . . . . . . . . . . . . . . .... ...... ... . . . . . . . . . . ...... . .. . . . . . . . . . . .. . . . . .... . . . . 272 BREAKTHROUG H PRODUC TS . . . . . . . . . . . . . . . . . ...... . . . . . . . . . . . ....... . . . . . . . . . . . . . . .. . . . . . . . . . 273 lmmunomodulators. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 Enzyme Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274 Receptor Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 Inhibitors of Cellular Proliferation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 AGR ICULTUR AL PRODUCTS . . . . . . . . . .... .. ..... . .. . . . . . . . . . . . ..... .... . . . . . . . . . .. . . . . . . . . . . . . . 278 N EWLY R ECOGNIZED AC TIVITIES OF K NOWN COMPOUNDS . . . . . . .... . . . . . . . . . . . 280 CHEM IC ALLY MODIFIED M ICROB IAL PRODUCTS . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . 281 COMMON S TRUCTURAL THEMES . . . . . . . . . .... .. ... . .. . . . . . .. . . . .. . . . .. . . . . . .. . . . . 282 Macrolides . . . .. . .. .. .. . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . ....... . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . 282 Cyclic Peptides . . . . . . . . . . . . . . . ... . . . .. . . . . . . . . . . . . ... . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 283 RATION AL SCREENING . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . 284 Assay Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 Choice of Microorganisms . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286 FUTURE TRENDS .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289

BIOACTIVE MICROBIAL PRODUCTS: Focus upon Mechanism of Action

The GNS1 gene product is required for the synthesis of 1,3-beta-glucan in vitro, since mutations in this gene result in exhibit an 80 to 90% reduction in 1,3-beta-glucan synthase specific activity. gns1 mutant strains display a pleiotropic phenotype including resistance to a pneumocandin B0 analog (L-733,560), slow growth, and mating and sporulation defects. The gns1-1 mutation was genetically mapped to within 1.35 centimorgans from the MAT locus on chromosome III. The wild-type GNS1 gene was isolated by complementing the pneumocandin resistance phenotype of the gns1-1 mutation and by hybridization with a chromosome III-derived sequence being used as a probe. The nucleotide sequence of GNS1 was determined and compared with the homologous region of the chromosome. The genetic and nucleotide sequence analyzes revealed that GNS1 and the open reading frame, YCR34 [S. Oliver, Q. van der Aart, M. Agostoni-Carbone, and the Chromosome III Sequencing Group, Nature (London) 357:38-46, 1992], represent identical loci in the genome. Cells deleted for GNS1 are viable but exhibit slow growth as well as the pleiotropic phenotype of the gns1 mutants. The putative protein product is predicted to be an integral membrane protein with five transmembrane helices displaying an exoplasmic orientation for the N terminus and a cytoplasmic orientation for the C terminus. This protein may be a subunit of 1,3-beta-glucan synthase.

Cloning and characterization of GNS1: a Saccharomyces cerevisiae gene involved in synthesis of 1,3-beta-glucan in vitro.

The screening of microorganisms for the production of useful products continues to be an important aspect of biotechnology. Although advances in instrumentation, genetics, and microbial physiology are having an impact, screening programs are still primarily based on so-called classical techniques of enrichment and mutagenesis. One area that needs strengthening is the advancement of knowledge in microbial physiology. Recent surveys indicate that industry leaders see trained microbial physiologists as being the limiting factor in development of biotechnology in the coming decade. The largest impediment to development of new screening techniques is the ironic lack of programs specifically directed at developing new techniques. Too much emphasis is placed on using available techniques and relying on sheer labor and screening of vast numbers of organisms to produce novel products. In this respect, the Japanese are the exception and have proven that the establishment of new programs is worth the cost and effort. They are undoubtedly the world leaders in development of screening techniques and consequently the discovery of novel products. The isolation of microbes from novel and extreme environments holds tremendous promise in two areas. First, as Omura (46) and others (9, 48, 65) state, novel organisms will yield novel products. Second, such organisms serve as models for the understanding of structure and function that will facilitate the genetic manipulation of organisms and advance our ability to engineer novel enzymes. Hopefully such advances will enable genetic and protein engineering to have a greater impact on screening programs and techniques in the future. The earth holds a vast amount of varied and unique environments, from natural extremes such as high-altitude deserts and thermal springs, to manmade environments such as industrial-waste-treatment facilities, from which, with the appropriate methods and techniques, we may isolate and evaluate new potential products.

Techniques for Selection of Industrially Important Microorganisms

Screening for new microbial products by high-performance liquid chromatography using a photodiode array detector.

Production of nikkomycins by Streptomyces tendae is dependent on phosphate concentration, pH and the presence of precursors or regulatory factors in the medium. In a batch-feeding system the production of antibiotically active nikkomycins could be increased up to 3 g dm−3. The selective production of single compounds was possible by feeding precursors or using mutants of Streptomyces tendae. The whole qualitative and quantitative determination of nikkomycins was carried out with ion-pair reversed-phase high-performance liquid chromatography (h.p.l.c.).

Nikkomycins: Microbial inhibitors of chitin synthase

Nikkomycins: microbial inhibitors of chitin synthase

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Nikkomycins: Microbial inhibitors of chitin synthase

Nikkomycins: microbial inhibitors of chitin synthase