Biosynthesis of a Natural Polyketide-Isoprenoid Hybrid Compound, Furaquinocin A: Identification and Heterologous Expression of the Gene Cluster

Kawasaki, Takashi; Hayashi, Yutaka; Kuzuyama, Tomohisa; Furihata, Kazuo; Itoh, Nobuhide; Seto, Haruo; Dairi, Tohru

doi:10.1128/jb.188.4.1236-1244.2006

Cited by 80 publications

(86 citation statements)

References 47 publications

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“…Fur7, encoded in the furaquinocin A gene cluster of Streptomyces sp. strain KO-3988 [22], and NapT8 and NapT9, encoded in the napyradiomycin gene cluster in S. aculeolatus and Streptomyces sp. strain CNQ-525 [23], possess significant sequence similarity to NphB, Fnq26 and Fnq28 (see Fig.…”

Section: A Growing Family Of Abba Ptasesmentioning

confidence: 99%

The ABBA family of aromatic prenyltransferases: broadening natural product diversity

Tello

Kuzuyama²,

Heide³

et al. 2008

Cell. Mol. Life Sci.

128

155

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Aromatic prenyltransferases (PTases) catalyze the transfer of a C5 (dimethylallyl), C10 (geranyl) or C15 (farnesyl) prenyl group derived from the corresponding isoprenyl diphosphate metabolites onto a variety of electron-rich aromatic acceptors. Prenyl groups appear in a wide variety of bioactive natural products of microbial and plant origin, including amino acids, stilbenes, alkaloids, polyketides and phenylpropanoids such as flavonoids, creating natural product hybrids with altered or enhanced bioactivities. Prenylation of flavonoids enhances some of the desirable pharmacological properties of these plant compounds [1], as demonstrated for apigenin and liquiritigenin [2]. Prenylation appears in many cases to provide a higher level of bioactivity compared to the non-prenylated precursor, often by increasing affinity for biological membranes and interactions with cellular targets [3]. With the recent identification of these enzymes there is increased interest in the role of these regiospecific catalysts in expanding the diversity and bioactivities of several important classes of natural products in vivo and in vitro.One way in which PTases can be categorized depends on whether they catalyze the synthesis of isoprenyl diphosphates, the prenylation of a protein or the prenylation of an aromatic substrate. Isoprenyl diphosphate synthases catalyze the chain elongation of an allylic isoprenyl diphosphate substrate by reaction with isopentenyl diphosphate [4]. Protein PTases transfer a geranyl-geranyl or farnesyl group to the Cys residue on a CaaX motif at the C-terminus of several proteins to facilitate membrane anchoring in eukaryotes and possibly archaea [5]. Small-molecule aromatic PTases constituting the third category can be subdivided into membrane-associated and functionally soluble PTases. Membrane-associated PTases contain a characteristic (N/D)DXXD Mg 2+ -diphosphate binding motif which is also found in the isoprenyl diphosphate synthases and are involved e.g. in the biosynthesis of ubiquinones and © Birkhäuser Verlag, Basel, 2008 Richard@salk.edu. [6], in the biosynthesis of membrane lipids in archaea [7] and in the formation of plant secondary metabolites [8].The functionally soluble PTases do not possess an obvious Mg 2+ -diphosphate binding motif. Moreover, most of the currently known soluble aromatic PTases segregate into two subgroups based on their primary sequence similarity and on the small-molecule substrates they accept for prenylation. The first subgroup commonly prenylates indole-containing ring systems. Examples of these PTases include the fungal enzymes FgaPT1 and FgaPT2 involved in the biosynthesis of fumigaclavin C [9], as well as the newly discovered N-reverse PTase CdpNPT [10] and the 7-dimethylallyl-tryptophan synthase Afu3 g12930 [11]. LtxC, which is involved in the biosynthesis of lyngbyatoxins obtained from the cyanobacteria Lyngbya majuscula [12], also prenylates an indole-containing ring system but shares no sequence similaritywith the fungal enzymes named above.The second subg...

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Section: A Growing Family Of Abba Ptasesmentioning

confidence: 99%

The ABBA family of aromatic prenyltransferases: broadening natural product diversity

Tello

Kuzuyama²,

Heide³

et al. 2008

Cell. Mol. Life Sci.

128

155

View full text Add to dashboard Cite

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“…These were identified as 1, 2 and 3, respectively (Figure 1), where 3 was the major metabolite. The production of 3 as a major metabolite is also reported by heterologous expression of fur1 to fur21 on S. lividans 14 and S. albus. 15 Given the findings of heterologous studies and our observations that FQ production was enhanced simply by the introduction of fur22 to the strain NRM1, Fur22 can be considered a positive regulator of FQ biosynthesis.…”

Section: Resultsmentioning

confidence: 86%

“…14,15 By taking advantage of known FQ gene cluster from original producer strain S. sp. KO-3988, 14 we could find a highly homologous gene cluster from S. reveromyceticus SN-593.…”

Section: Biosynthesis Of 1 Andmentioning

confidence: 99%

“…14,15 By taking advantage of known FQ gene cluster from original producer strain S. sp. KO-3988, 14 we could find a highly homologous gene cluster from S. reveromyceticus SN-593. On the basis of the structures of 1, 2 and 3, and gene annotations (Supplementary Table 1), it is expected that three rounds of oxidation at C-14 of 3 will Novel furaquinocins from Streptomyces reveromyceticus SN-593 S Panthee et al lead to the formation of carboxyl group (1) by a P450 (Fur8), whereas carboxamide formation from 1 by an aminotransferase (Fur3) will lead to 2.…”

Section: Biosynthesis Of 1 Andmentioning

confidence: 99%

“…KO-3988, 11 have cytocidal activities without antibacterial activity. So far, eight analogues of these polyketide isoprenoid hybrid compounds ( Figure 1) [11][12][13] and their gene cluster 14 have been identified. However, no new analogues have been described since the discovery of FQ two decades ago.…”

Section: Introductionmentioning

confidence: 99%

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Furaquinocins I and J: novel polyketide isoprenoid hybrid compounds from Streptomyces reveromyceticus SN-593

et al. 2011

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Two novel furaquinocin (FQ) analogues, I (1) and J (2), were isolated from Streptomyces reveromyceticus SN-593 strain NRM2. Their structures were elucidated by MS and NMR analyses. Similar to the previously described FQ D (3), both 1 and 2 possessed a dihydrofuran ring fused to a polyketide naphthoquinone skeleton. The main difference between 1, 2 and 3 was the type of residue attached to C-13; these were a carboxyl, a carboxamide and a methyl residue, respectively. INTRODUCTIONThe majority of bioactive compounds used as drugs and bioprobes originally derive from the secondary metabolites of microorganisms. Genome sequence analyses have shown that the number of bioactive compounds isolated from Streptomyces spp. is much lower than the number of gene clusters harbored by each species. [1][2][3] This indicates that the majority of gene clusters are either not expressed, or are only minimally expressed, under standard laboratory conditions. To discover novel natural products that are normally expressed at a very low level, we have been performing a systematic isolation of secondary metabolites. As a result, we isolated verticilactam 4 from Streptomyces spiroverticillatus JC-8444, a tautomycin producer, 5 and 6-dimethylallylindole-3-carbaldehyde 6 from S. reveromyceticus SN-593, a reveromycin producer. 7 In addition, from S. reveromyceticus SN-593, we detected metabolites showing UV spectra similar to furaquinocin (FQ), but different mass from the reported FQs. Consistent with the finding, we could annotate an FQ biosynthetic gene cluster from the genome draft sequence. However, with the quantity produced by wild type strain, it was not possible to isolate and determine the structure. So, in order to improve the production of novel FQ derivatives, we performed the expression of pathway-specific regulatory genes associated with the FQ biosynthetic gene cluster. Activation of pathwayspecific positive regulatory gene is commonly used for augmentation of secondary metabolites in Streptomyces. [8][9][10] FQs, originally isolated from the culture broth of Streptomyces sp. 11 have cytocidal activities without antibacterial activity. So far, eight analogues of these polyketide isoprenoid hybrid compounds (Figure 1) [11][12][13] and their gene cluster 14 have been identified.

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Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media

Willrodt

David

Cornelissen

et al. 2014

Biotechnology Journal

105

111

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The efficiency and productivity of cellular biocatalysts play a key role in the industrial synthesis of fine and bulk chemicals. This study focuses on optimizing the synthesis of (S)-limonene from glycerol and glucose as carbon sources using recombinant Escherichia coli. The cyclic monoterpene limonene is extensively used in the fragrance, food, and cosmetic industries. Recently, limonene also gained interest as alternative jet fuel of biological origin. Key parameters that limit the (S)-limonene yield, related to genetics, physiology, and reaction engineering, were identified. The growth-dependent production of (S)-limonene was shown for the first time in minimal media. E. coli BL21 (DE3) was chosen as the preferred host strain, as it showed low acetate formation, fast growth, and high productivity. A two-liquid phase fed-batch fermentation with glucose as the sole carbon and energy source resulted in the formation of 700 mg L(org) (-1) (S)-limonene. Specific activities of 75 mU g(cdw) (-1) were reached, but decreased relatively quickly. The use of glycerol as a carbon source resulted in a prolonged growth and production phase (specific activities of ≥50 mU g(cdw) (-1) ) leading to a final (S)-limonene concentration of 2,700 mg L(org) (-1) . Although geranyl diphosphate (GPP) synthase had a low solubility, its availability appeared not to limit (S)-limonene formation in vivo under the conditions investigated. GPP rerouting towards endogenous farnesyl diphosphate (FPP) formation also did not limit (S)-limonene production. The two-liquid phase fed-batch setup led to the highest monoterpene concentration obtained with a recombinant microbial biocatalyst to date.

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Biosynthesis of a Natural Polyketide-Isoprenoid Hybrid Compound, Furaquinocin A: Identification and Heterologous Expression of the Gene Cluster

Cited by 80 publications

References 47 publications

The ABBA family of aromatic prenyltransferases: broadening natural product diversity

The ABBA family of aromatic prenyltransferases: broadening natural product diversity

Furaquinocins I and J: novel polyketide isoprenoid hybrid compounds from Streptomyces reveromyceticus SN-593

Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media

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