Proof that the actVI genetic region of Streptomyces coelicolor A3(2) is involved in stereospecific pyran ring formation in the biosynthesis of actinorhodin

Ichinose, Koji; Surti, Chandres M.; Taguchi, Tanezo; Malpartida, Francisco; Booker‐Milburn, Kevin I.; Stephenson, G. R.; Ebizuka, Yutaka; Da, Hopwood

doi:10.1016/s0960-894x(99)00011-6

Cited by 48 publications

(22 citation statements)

References 14 publications

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“…To accomplish this, we cloned the C-3 ketoreductase gene, encoded by act VI-ORF1, onto pRM5, yielding the plasmid pJF6 (Table 1). As predicted, S. coelicolor CH999/pJF6/pBOOST* yielded 5a after cyclization and loss of water (Figure S16) 5,19 .…”

Section: Resultssupporting

confidence: 79%

Engineered biosynthesis of the antiparasitic agent frenolicin B and rationally designed analogs in a heterologous host

2011

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The polyketide antibiotic frenolicin B harbors a biosynthetically intriguing benzoisochromanequinone core, and has been shown to exhibit promising antiparasitic activity against Eimeria tenella. To facilitate further exploration of its chemistry and biology, we constructed a biosynthetic route to frenolicin B in the heterologous host Streptomyces coelicolor CH999, despite the absence of key enzymes in the identified frenolicin gene cluster. Together with our understanding of the underlying polyketide biosynthetic pathway, this heterologous production system was exploited to produce analogs modified at the C15 position. Both the natural product and these analogs inhibited the growth of Toxoplasma gondii in a manner that reveals sensitivity to the length of the C15 substituent. The ability to construct a functional biosynthetic pathway, despite a lack of genetic information, illustrates the feasibility of a modular approach to engineering medicinally relevant polyketide products.

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Section: Resultssupporting

confidence: 79%

Engineered biosynthesis of the antiparasitic agent frenolicin B and rationally designed analogs in a heterologous host

2011

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“…It is noteworthy that ecaD is similar to oxidoreductases (ActVI-ORF2 and ActVI-ORF4), and ecaB to a monooxygenase (ActVA-ORF6), that catalyze later steps in the Act biosynthetic pathway. These tailoring reactions lead to the production of a series of biologically active metabolites and finally Act (33,41,FIG. 5.…”

Section: Discussionmentioning

confidence: 99%

Expression of the Streptomyces coelicolor SoxR Regulon Is Intimately Linked with Actinorhodin Production

et al. 2010

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The [2Fe-2S]-containing transcription factor SoxR is conserved in diverse bacteria. SoxR is traditionally known as the regulator of a global oxidative stress response in Escherichia coli, but recent studies suggest that this function may be restricted to enteric bacteria. In the vast majority of nonenterics, SoxR is predicted to mediate a response to endogenously produced redox-active metabolites. We have examined the regulation and function of the SoxR regulon in the model antibiotic-producing filamentous bacterium Streptomyces coelicolor. Unlike the E. coli soxR deletion mutant, the S. coelicolor equivalent is not hypersensitive to oxidants, indicating that SoxR does not potentiate antioxidant defense in the latter. SoxR regulates five genes in S. coelicolor, including those encoding a putative ABC transporter, two oxidoreductases, a monooxygenase, and a possible NAD-dependent epimerase/dehydratase. Expression of these genes depends on the production of the benzochromanequinone antibiotic actinorhodin and requires intact [2Fe-2S] clusters in SoxR. These data indicate that actinorhodin, or a redox-active precursor, modulates SoxR activity in S. coelicolor to stimulate the production of a membrane transporter and proteins with homology to actinorhodin-tailoring enzymes. While the role of SoxR in S. coelicolor remains under investigation, these studies support the notion that SoxR has been adapted to perform distinct physiological functions to serve the needs of organisms that occupy different ecological niches and face different environmental challenges.

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“…The 3S-selective reductase of S. coelicolor (designated RED1) was proven to be the product from actVI-Orf1 [78]. There was, however, no analogous protein encoded in the gra gene cluster in S. violaceoruber.…”

Section: Granaticinmentioning

confidence: 99%

Bioactive C-Glycosides from Bacterial Secondary Metabolism

Hultin

2005

CTMC

122

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C-Glycosides are commonly regarded as unusual structures, but they are far more prevalent among natural products than is imagined. This review discusses the C-glycosidic compounds produced by various bacteria, particularly the "biosynthetically talented" Streptomyces. The major structure types are presented, along with brief descriptions of the known biological and pharmacological properties of the compounds. Recent work has uncovered the genetic basis for the biosynthesis of several bacterial C-glycosides, and emphasis is placed on those cases where it has been possible to identify (at least provisionally) the C-glycosyltransferase in the pathway. Prospects for biosynthetic engineering, combinatorial biosynthesis, or glycorandomization in C-glycosidic natural products are briefly discussed.

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Proof that the actVI genetic region of Streptomyces coelicolor A3(2) is involved in stereospecific pyran ring formation in the biosynthesis of actinorhodin

Cited by 48 publications

References 14 publications

Engineered biosynthesis of the antiparasitic agent frenolicin B and rationally designed analogs in a heterologous host

Engineered biosynthesis of the antiparasitic agent frenolicin B and rationally designed analogs in a heterologous host

Expression of the Streptomyces coelicolor SoxR Regulon Is Intimately Linked with Actinorhodin Production

Bioactive C-Glycosides from Bacterial Secondary Metabolism

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