Industrial Microbiology

Demain, Arnold L.

doi:10.1126/science.6946560

Cited by 96 publications

(38 citation statements)

References 34 publications

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“…(Arai, 1976;Goodfellow et al, 1988;Demain, 1981). These bacteria have, for the most part, been obtained from soil samples in various parts of the world (Waksman, 1967).…”

Section: Discussionmentioning

confidence: 99%

Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp.

et al. 2004

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Coronamycin is a complex of novel peptide antibiotics with activity against pythiaceous fungi and the human fungal pathogen Cryptococcus neoformans. It is also active against the malarial parasite, Plasmodium falciparum, with an IC 50 of 9?0 ng ml "1. Coronamycin is produced by a verticillate Streptomyces sp. isolated as an endophyte from an epiphytic vine, Monstera sp., found in the Manu region of the upper Amazon of Peru. Bioassay-guided fractionation of the fermentation broths of this endophyte on silica gel and HPLC chromatography yielded two principal, inseparable, peptides with masses of 1217?9 and 1203?8 Da. Three other minor, but related components, are also present in the preparation. Amino acid analysis of coronamycin revealed residues of component 1, component 2, methionine, tyrosine and leucine at a ratio of 2 : 2 : 1 : 1 : 3. Other compounds with antifungal activities are also produced by this endophytic streptomycete.

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“…(Arai, 1976;Goodfellow et al, 1988;Demain, 1981). These bacteria have, for the most part, been obtained from soil samples in various parts of the world (Waksman, 1967).…”

Section: Discussionmentioning

confidence: 99%

Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp.

et al. 2004

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“…However, these data vividly demonstrate the effectiveness of the rational genetic manipulation of a natural biosynthetic pathway as a means of enhancing the titers of important drug leads. This process stands in contrast to the lengthy, empirical strain improvement programs that have traditionally been implemented for the generation of overproducing strains (2).…”

Section: To 10mentioning

confidence: 99%

Engineered Streptomyces platensis Strains That Overproduce Antibiotics Platensimycin and Platencin

Smanski¹,

Peterson

Rajski

et al. 2009

Antimicrob Agents Chemother

120

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Platensimycin, which is isolated from Streptomyces platensis MA7327, and platencin, which is isolated from S. platensis MA7339, are two recently discovered natural products that serve as important antibiotic leads. Here we report on the identification of S. platensis MA7327 as a dual producer of both platensimycin and platencin. A PCR-based approach was used to locate and clone the locus involved in platensimycin and platencin production, including ptmR1, which encodes a putative GntR-like transcriptional regulator. Deletion of this gene from the producing organism allowed us to isolate strains that overproduce platensimycin and platencin with yields of 323 ؎ 29 mg/liter and 255 ؎ 30 mg/liter, respectively. These results illustrate the effectiveness of genetic manipulation for the rational engineering of improvements in titers.The discovery of platensimycin (16,20) and platencin (8,19) as members of an entirely new class of antibacterial antibiotics with a mode of action not exploited by current drugs represents an important step in the fight against antibiotic resistance (Fig. 1a). Both compounds are potent and selective inhibitors of bacterial fatty acid synthesis. Platensimycin specifically targets the elongation ␤-ketoacyl-acyl carrier protein (ACP) synthase I/II, FabF/B (20), while platencin has a dual mode of action and targets both FabF/B and the initiation ␤-ketoacyl-ACP synthase III, FabH (19). Both natural products are effective against a broad spectrum of gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and show no cross-resistance with other classes of commercially available antibiotics (19). Although platensimycin has proven effective in clearing methicillin-resistant S. aureus infection from a mouse model, the high doses and the suboptimal delivery system required highlight the need for further refinement of its structure prior to the conduct of clinical trials. Multiple total syntheses of both compounds, as well as numerous analogs, underscore the excitement generated by these compounds as leads for novel antiinfectives (10-14, 18).Platensimycin was isolated from Streptomyces platensis MA7327 at a yield of 2 to 4 mg/liter (16), and platencin was isolated from Streptomyces platensis MA7339 at a yield of 1 mg/liter (8). Subsequent fermentation optimization has led to a recent report that S. platensis MA7327 produced platensimycin at yields up to 56 mg/liter (6). No such improvement of the platencin titer has been reported to date. Strains capable of producing higher yields of platensimycin or platencin, or both, will facilitate the development of these promising leads into clinical agents. Toward this end, we have determined an appropriate set of protocols for the genetic manipulation of platensimycinproducing strain S. platensis MA7327 and exploited the regulatory mechanism of platensimycin and platencin biosynthesis to engineer S. platensis strains that are capable of overproducing both platensimycin and platencin at titers of 32...

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“…Micro-organisms have long served mankind by virtue of the myriad of enzymes and secondary products, including pharmaceuticals, that they make (Demain, 1981). However, only a relatively small number of microbes are used directly in human applications such as the production of bread, cheese and alcoholic beverages, and environmental clean-up activities.…”

Section: Introductionmentioning

confidence: 99%

Volatile antimicrobials from Muscodor crispans, a novel endophytic fungus

et al. 2010

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Muscodor crispans is a recently described novel endophytic fungus of Ananas ananassoides (wild pineapple) growing in the Bolivian Amazon Basin. The fungus produces a mixture of volatile organic compounds (VOCs); some of the major components of this mixture, as determined by GC/MS, are propanoic acid, 2-methyl-, methyl ester; propanoic acid, 2-methyl-; 1-butanol, 3-methyl-;1-butanol, 3-methyl-, acetate; propanoic acid, 2-methyl-, 2-methylbutyl ester; and ethanol. The fungus does not, however, produce naphthalene or azulene derivatives as has been observed with many other members of the genus Muscodor. The mixture of VOCs produced by M. crispans cultures possesses antibiotic properties, as does an artificial mixture of a majority of the components. The VOCs of the fungus are effective against a wide range of plant pathogens, including the fungi Pythium ultimum, Phytophthora cinnamomi, Sclerotinia sclerotiorum and Mycosphaerella fijiensis (the black sigatoka pathogen of bananas), and the serious bacterial pathogen of citrus, Xanthomonas axonopodis pv. citri. In addition, the VOCs of M. crispans killed several human pathogens, including Yersinia pestis, Mycobacterium tuberculosis and Staphylococcus aureus. Artificial mixtures of the fungal VOCs were both inhibitory and lethal to a number of human and plant pathogens, including three drug-resistant strains of Mycobacterium tuberculosis. The gaseous products of Muscodor crispans potentially could prove to be beneficial in the fields of medicine, agriculture, and industry.

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Industrial Microbiology

Cited by 96 publications

References 34 publications

Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp.

Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp.

Engineered Streptomyces platensis Strains That Overproduce Antibiotics Platensimycin and Platencin

Volatile antimicrobials from Muscodor crispans, a novel endophytic fungus

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