ArticleApplied and environmental microbiology2011
Reconstitution of the FK228 biosynthetic pathway reveals cross talk between modular polyketide synthases and fatty acid synthase.
Article in Applied and environmental microbiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
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- Covalent warhead assembly in fostriecin biosynthesis involves malonylation-lactonisation by a bifunctional thioesterase and enzymatic demalonylation.Nature communications · 2026Article
- Engineered romidepsin biosynthetic pathways in Escherichia coli Nissle 1917 improve the efficacy of bacteria-mediated cancer therapy.PLoS biology · 2026Article
- Simultaneous DHA and organic selenium production by Schizochytrium sp.: a theoretical basis.Scientific reports · 2023Article
- Crosstalk between primary and secondary metabolism: Interconnected fatty acid and polyketide biosynthesis in prokaryotes.Bioorganic & medicinal chemistry letters · 2023Review
- Recent developments in the identification and biosynthesis of antitumor drugs derived from microorganisms.Engineering microbiology · 2022Review
- Origin and bioactivities of thiosulfinated FK228.MedChemComm · 2019Article
- Discovery of 16-Demethylrifamycins by Removing the Predominant Polyketide Biosynthesis Pathway inApplied and environmental microbiology · 2019Article
- Genomics-guided discovery of a new and significantly better source of anticancer natural drug FK228.Synthetic and systems biotechnology · 2018Article
- Biosynthesis of t-Butyl in Apratoxin A: Functional Analysis and Architecture of a PKS Loading Module.ACS chemical biology · 2018Article
- The secreted metabolome ofProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Discovery of a new diol-containing polyketide by heterologous expression of a silent biosynthetic gene cluster from Streptomyces lavendulae FRI-5.Journal of industrial microbiology & biotechnology · 2018Article
- Mechanistic studies of DepR in regulating FK228 biosynthesis in Chromobacterium violaceum no. 968.PloS one · 2018Article
- Investigating the Biosynthesis of Natural Products from Marine Proteobacteria: A Survey of Molecules and Strategies.Marine drugs · 2017Review
- Direct Capture Technologies for Genomics-Guided Discovery of Natural Products.Current topics in medicinal chemistry · 2016Review
- Disulfide cross-linked micelles of novel HDAC inhibitor thailandepsin A for the treatment of breast cancer.Biomaterials · 2015Article
- Engineered Production of Tryprostatins inJacobs journal of biotechnology and bioengineering · 2015Article
- Genetic determinants of reutericyclin biosynthesis in Lactobacillus reuteri.Applied and environmental microbiology · 2015Article
- Identification and characterization of the spiruchostatin biosynthetic gene cluster enable yield improvement by overexpressing a transcriptional activator.Journal of industrial microbiology & biotechnology · 2014Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Functional cross talk between fatty acid biosynthesis and secondary metabolism has been discovered in several cases in microorganisms; none of them, however, involves a modular biosynthetic enzyme. Previously, we reported a hybrid modular nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) pathway for the biosynthesis of FK228 anticancer depsipeptide in Chromobacterium violaceum strain 968. This pathway contains two PKS modules on the DepBC enzymes that lack a functional acyltransferase (AT) domain, and no apparent AT-encoding gene exists within the gene cluster or its vicinity. We report here that, through reconstitution of the FK228 biosynthetic pathway in Escherichia coli cells, two essential genes, fabD1 and fabD2, both encoding a putative malonyl coenzyme A (CoA) acyltransferase component of the fatty acid synthase complex, are positively identified to be involved in FK228 biosynthesis. Either gene product appears sufficient to complement the AT-less PKS modules on DepBC for polyketide chain elongation. Concurrently, a gene (sfp) encoding a putative Sfp-type phosphopantetheinyltransferase was identified to be necessary for FK228 biosynthesis as well. Most interestingly, engineered E. coli strains carrying variable genetic components produced significant levels of FK228 under both aerobic and anaerobic cultivation conditions. Discovery of the trans complementation of modular PKSs by housekeeping ATs reveals natural product biosynthesis diversity. Moreover, demonstration of anaerobic production of FK228 by an engineered facultative bacterial strain validates our effort toward the engineering of novel tumor-targeting bioagents.
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