ArticleApplied and environmental microbiology2008
Enhanced heterologous production of desosaminyl macrolides and their hydroxylated derivatives by overexpression of the pikD regulatory gene in Streptomyces venezuelae.
Article in Applied and environmental microbiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential.Chembiochem : a European journal of chemical biology · 2026Review
- Optimized production of concanamycins using a rational metabolic engineering strategy.Metabolic engineering · 2025Article
- Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization.Beilstein journal of organic chemistry · 2024Review
- Chemoenzymatic synthesis of fluorinated polyketides.Nature chemistry · 2022Article
- Engineering actinomycetes for biosynthesis of macrolactone polyketides.Microbial cell factories · 2019Review
- Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway.Nature communications · 2016Article
- Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin, and ketomethymycin.Journal of the American Chemical Society · 2013Article
- Heterologous expression and manipulation of three tetracycline biosynthetic pathways.Angewandte Chemie (International ed. in English) · 2012Article
- Roles of fkbN in positive regulation and tcs7 in negative regulation of FK506 biosynthesis in Streptomyces sp. strain KCTC 11604BP.Applied and environmental microbiology · 2012Article
- Development of a Streptomyces venezuelae-based combinatorial biosynthetic system for the production of glycosylated derivatives of doxorubicin and its biosynthetic intermediates.Applied and environmental microbiology · 2011Article
- Improvement of secondary metabolite production in Streptomyces by manipulating pathway regulation.Applied microbiology and biotechnology · 2010Review
- Streptomycetes: Surrogate hosts for the genetic manipulation of biosynthetic gene clusters and production of natural products.Biotechnology advancesReview
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To elevate the production level of heterologous polyketide in Streptomyces venezuelae, an additional copy of the positive regulatory gene pikD was introduced into the pikromycin (Pik) polyketide synthase (PKS) deletion mutant of S. venezuelae ATCC 15439 expressing tylosin PKS genes. The resulting mutant strain showed enhanced production of both tylactone (TL) and desosaminyl tylactone (DesTL) of 2.7- and 17.1-fold, respectively. The notable increase in DesTL production strongly suggested that PikD upregulates the expression of the desosamine (des) biosynthetic gene cluster. In addition, two hydroxylated forms of DesTL were newly detected from the extract of this mutant. These hydroxylated forms presumably resulted from a PikD-dependent increase in expression of the pikC gene that encodes P450 hydroxylase. Gene expression analysis by reverse transcriptase PCR and bioconversion experiments of 10-deoxymethynolide, narbonolide, and TL into the corresponding desosaminyl macrolides indicated that PikD is a positive regulator of the des and pikC genes, as well as the Pik PKS genes. These results demonstrate the role of PikD as a pathway-specific positive regulator of the entire Pik biosynthetic pathway and its usefulness in the development of a host-vector system for efficient heterologous production of desosaminyl macrolides and novel hydroxylated compounds.
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