Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

Guo, Chun Jun; Sun, Wei; Bruno, Kenneth S.; Oakley, Berl R; Keller, Nancy P.; Wang, Clay C. C.

doi:10.1039/c5sc01058f

Cited by 32 publications

(27 citation statements)

References 36 publications

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“…). Until now, examples of such non‐linear biosynthetic pathways that include redundant key enzymes are limited and have been only recently reported for some Aspergillus species (Forseth et al ., ; Guo et al ., ; Throckmorton et al ., ).…”

Section: Discussionmentioning

confidence: 99%

“…7). Until now, examples of such non-linear biosynthetic pathways that include redundant key enzymes are limited and have been only recently reported for some Aspergillus species (Forseth et al, 2013;Guo et al, 2015;Throckmorton et al, 2015). BcPKS12 is expressed during sclerotial development in DD and provides the precursor T4HN for further conversion to DHN.…”

Section: Discussionmentioning

confidence: 99%

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DHN melanin biosynthesis in the plant pathogenic fungus Botrytis cinerea is based on two developmentally regulated key enzyme (PKS)‐encoding genes

Schumacher

2015

Molecular Microbiology

140

161

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SummaryBotrytis cinerea is the causal agent of gray mold disease in various plant species and produces grayish macroconidia and/or black sclerotia at the end of the infection cycle. It has been suggested that the pigmentation is due to the accumulation of 1,8-dihydroxynaphthalene (DHN) melanin. To unravel its basis and regulation, the putative melanogenic and regulatory genes were identified and functionally characterized. Unlike other DHN melanin-producing fungi, B. cinerea and other Leotiomycetes contain two key enzyme (PKS)-encoding enzymes. Bcpks12 and bcpks13 are developmentally regulated and are required for melanogenesis in sclerotia and conidia respectively. BcYGH1 converts the BcPKS13 product and contributes thereby to conidial melanogenesis. In contrast, enzymes acting downstream in conversion of the PKS products (BcBRN2, BcSCD1 and BcBRN1) are required for both, sclerotial and conidial melanogenesis, suggesting that DHN melanogenesis in B. cinerea follows a non-linear pathway that is rather unusual for secondary metabolic pathways. Regulation of the melanogenic genes involves three pathway-specific transcription factors (TFs) that are clustered with bcpks12 or bcpks13 and other developmental regulators such as light-responsive TFs. Melanogenic genes are dispensable in vegetative mycelia for proper growth and virulence. However, DHN melanin is considered to contribute to the longevity of the reproduction structures.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DHN melanin biosynthesis in the plant pathogenic fungus Botrytis cinerea is based on two developmentally regulated key enzyme (PKS)‐encoding genes

Schumacher

2015

Molecular Microbiology

140

161

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“…In an unexpected twist, we find that both the tpc and enc clusters contribute to the synthesis of endocrocin. To our knowledge, only two prior studies have described two physically discrete clusters contributing to the synthesis of the same metabolite in one fungal species (Forseth et al ., 2013; Guo et al ., 2015). This finding is in contrast to the recently discovered phenomenon of superclusters, in which a single co-regulated cluster can produce two distinct metabolites (e.g.…”

Section: Discussionmentioning

confidence: 99%

Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus

Throckmorton

Lim

Kontoyiannis

et al. 2015

Environmental Microbiology

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Summary Filamentous fungi are renowned for the production of bioactive secondary metabolites. Typically, one distinct metabolite is generated from a specific secondary metabolite cluster. Here, we characterize the newly described trypacidin (tpc) cluster in the opportunistic human pathogen Aspergillus fumigatus. We find that this cluster as well as the previously characterized endocrocin (enc) cluster both contribute to the production of the spore metabolite endocrocin. Whereas trypacidin is eliminated when only tpc cluster genes are deleted, endocrocin production is only eliminated when both the tpc and enc non-reducing polyketide synthase-encoding genes, tpcC and encA, respectively, are deleted. EncC, an anthrone oxidase, converts the product released from EncA to endocrocin as a final product. In contrast, endocrocin synthesis by the tpc cluster likely results from incomplete catalysis by TpcK (a putative decarboxylase), as its deletion results in a nearly 10-fold increase in endocrocin production. We suggest endocrocin is likely a shunt product in all related non-reducing polyketide synthase clusters containing homologues of TpcK and TpcL (a putative anthrone oxidase), e.g. geodin and monodictyphenone. This finding represents an unusual example of two physically discrete secondary metabolite clusters generating the same natural product in one fungal species by distinct routes.

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“…glycosylate or prenylate) the secondary metabolite with chemical modifications generating further chemotypes [60], which would be hard to predict by bioinformatics. A further layer of complexity is added by the fact that two distinct key enzymes might synthesize the same secondary metabolite (as in the case of the two NRPS-like proteins encoded by atmelA and apvA in A. terreus, which both produce aspulvinone E that, depending on the cell type, is converted into melanin or aspulvinones if localised into the conidia or hyphae, respectively [61]). Moreover, some key enzymes can participate in the "natural combinatorial biosynthesis" of several secondary metabolites (as in the synthesis of three pyrrolamide antibiotics by two BGCs in Streptomyces netropsis DSM40864, i.e.…”

Section: A Shot In the Dark: Approaches To Activate The Silent Microbmentioning

confidence: 99%

From Axenic to Mixed Cultures: Technological Advances Accelerating a Paradigm Shift in Microbiology

Nai

Meyer

2018

Trends in Microbiology

100

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Since the onset of microbiology in the late 19th century, scientists have been growing microorganisms almost exclusively as pure cultures, resulting in a limited and biased view of the microbial world. Only a paradigm shift in cultivation techniques - from axenic to mixed cultures - can allow a full comprehension of the (chemical) communication of microorganisms, with profound consequences for natural product discovery, microbial ecology, symbiosis, and pathogenesis, to name a few areas. Three main technical advances during the last decade are fueling the realization of this revolution in microbiology: microfluidics, next-generation 3D-bioprinting, and single-cell metabolomics. These technological advances can be implemented for large-scale, systematic cocultivation studies involving three or more microorganisms. In this review, we present recent trends in microbiology tools and discuss how these can be employed to decode the chemical language that microorganisms use to communicate.

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Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

Abstract: We have demonstrated that spatial regulation of the same product from two distinct genes generates metabolite diversity.

Cited by 32 publications

References 36 publications

DHN melanin biosynthesis in the plant pathogenic fungus Botrytis cinerea is based on two developmentally regulated key enzyme (PKS)‐encoding genes

DHN melanin biosynthesis in the plant pathogenic fungus Botrytis cinerea is based on two developmentally regulated key enzyme (PKS)‐encoding genes

Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus

From Axenic to Mixed Cultures: Technological Advances Accelerating a Paradigm Shift in Microbiology

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