UK-2A, B, C and D, Novel Antifungal Antibiotics from Streptomyces sp. 517-02. II. Structural Elucidation.

Hanafi, Muhammad; Shibata, Kozo; Ueki, Masaaki; Taniguchi, Makoto

doi:10.7164/antibiotics.49.1226

Cited by 43 publications

(32 citation statements)

References 2 publications

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“…) originally isolated from fermentation broths of the actinomycete Streptomyces sp. 517–02, extracts of which demonstrated strong antifungal activity against a broad spectrum of fungi in in vitro assays . Picolinamide chemistry delivers a novel biochemical mode of action for the cereals fungicide market involving inhibition of mitochondrial complex III via binding to the Q i ubiquinone binding site rather than to the Q o site targeted by the strobilurin class of fungicides and, as such, no target‐site‐based cross‐resistance to strobilurin fungicides would be anticipated (D. Young et al , manuscript in preparation).…”

Section: Introductionmentioning

confidence: 99%

Biological characterization of fenpicoxamid, a new fungicide with utility in cereals and other crops

Owen¹,

Yao²,

Myung³

et al. 2017

Pest Management Science

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BACKGROUNDThe development of novel highly efficacious fungicides that lack cross‐resistance is extremely desirable. Fenpicoxamid (Inatreq™ active) possesses these characteristics and is a member of a novel picolinamide class of fungicides derived from the antifungal natural product UK‐2A.RESULTSFenpicoxamid strongly inhibited in vitro growth of several ascomycete fungi, including Zymoseptoria tritici (EC50, 0.051 mg L−1). Fenpicoxamid is converted by Z. tritici to UK‐2A, a 15‐fold stronger inhibitor of Z. tritici growth (EC50, 0.0033 mg L−1). Strong fungicidal activity of fenpicoxamid against driver cereal diseases was confirmed in greenhouse tests, where activity on Z. tritici and Puccinia triticina matched that of fluxapyroxad. Due to its novel target site (Qi site of the respiratory cyt bc1 complex) for the cereals market, fenpicoxamid is not cross‐resistant to Z. tritici isolates resistant to strobilurin and/or azole fungicides. Across multiple European field trials Z. tritici was strongly controlled (mean, 82%) by 100 g as ha−1 applications of fenpicoxamid, which demonstrated excellent residual activity.CONCLUSIONSThe novel chemistry and biochemical target site of fenpicoxamid as well as its lack of cross‐resistance and strong efficacy against Z. tritici and other pathogens highlight the importance of fenpicoxamid as a new tool for controlling plant pathogenic fungi. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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Section: Introductionmentioning

confidence: 99%

Biological characterization of fenpicoxamid, a new fungicide with utility in cereals and other crops

Owen¹,

Yao²,

Myung³

et al. 2017

Pest Management Science

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“…The results are summarized in Table 1. All tested UK-2A analogues (1)(2)(3)(4)(5)(6), except 4, inhibited the growth of R. mucilaginosa IFO 0001, although the inhibitory activities of 1, 3, 5, and 6 were more than 100-1000 times less than that of UK-2A, demonstrating that the 9-membered dilactone moiety is not essential for such an weak antifungal activity, as reported for AA. 5 This is also consistent with our previous results.…”

mentioning

confidence: 59%

“…517-02 and is similar to antimycin A 3 (AA) in both structure and inhibitory activity toward electron transport at mitochondrial complex III. [1][2][3][4] Both UK-2A and AA consist of 9-membered dilactone rings linked via an amide bond to an aromatic acid moiety ( Fig. 1): UK-2A possesses a 3-hydroxy-4-methoxypicolinic moiety, while the AAs have 3-formamidosalicylic moieties, which are reported to be essential for complex III binding and inhibition of electron transfer between cytochromes b and c 1 in the mitochondrial respiratory chain.…”

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confidence: 99%

Structure–activity relationship studies on UK-2A, a novel antifungal antibiotic from Streptomyces sp. 517-02. Part 5: Roles of the 9-membered dilactone-ring moiety in respiratory inhibition

Usuki

Adachi

Fujita

et al. 2006

Bioorganic & Medicinal Chemistry Letters

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“…33 Fenpicoxamid is a derivative of the natural antifungal compound UK-2A, originally isolated from actinomycete Streptomyces sp. 517-02 fermentation broth, [49][50][51][52] extracts that demonstrated strong antifungal activity against a broad spectrum of fungi in in vitro assays (Fig. 6).…”

Section: Case Studiesmentioning

confidence: 99%

Natural products: a strategic lead generation approach in crop protection discovery

Lorsbach

Sparks

Cicchillo

et al. 2019

Pest Management Science

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With the anticipated population growth in the coming decades, the changing regulatory environment, and the continued emergence of resistance to commercial pesticides, there is a constant need to discover new lead chemistries with novel modes of action. We have established a portfolio of approaches to accelerate lead generation. One of these approaches capitalizes on the rich bioactivity of natural products (NPs), highlighted by the numerous examples of NP‐based crop protection compounds. Within Corteva Agriscience and the affiliated preceding companies, NPs have been a fruitful approach, for nearly three decades, to identifying and bringing to the market crop protection products inspired by or originating from NPs, . Included in these NP‐based crop protection products are the spinosyns family of insecticides, and those from more recent areas of NP‐based fungicidal chemistry, as highlighted in this perspective. © 2019 Society of Chemical Industry

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UK-2A, B, C and D, Novel Antifungal Antibiotics from Streptomyces sp. 517-02. II. Structural Elucidation.

Cited by 43 publications

References 2 publications

Biological characterization of fenpicoxamid, a new fungicide with utility in cereals and other crops

Biological characterization of fenpicoxamid, a new fungicide with utility in cereals and other crops

Structure–activity relationship studies on UK-2A, a novel antifungal antibiotic from Streptomyces sp. 517-02. Part 5: Roles of the 9-membered dilactone-ring moiety in respiratory inhibition

Natural products: a strategic lead generation approach in crop protection discovery

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