Microbial pigments: an untapped resource for teachers, artists and researchers

The journal PLoS Biology has launched a new series of articles on education "to present innovative approaches to teaching critical concepts, developments, and methods in biology." The title of the first article in the series is In Living Color: Bacterial Pigments as an Untapped Resource in the Classroom and Beyond.

From the article:

"Soil bacteria from the Streptomyces genus represent a source of interesting natural products that have been largely overlooked by artists, researchers, and teachers. This article is intended to encourage amateurs and professionals alike to explore this overflowing source of biopigments. Not only does this endeavor have the potential to lead us toward a fertile nexus between art and science, it may also lead to a more sustainable and environmentally friendly way to color the world around us in the future. The relevance of biopigments to many facets of science, technology, and society, makes this material an outstanding tool to engage students of varying academic interests across multiple age groups. Therefore, we encourage teachers of all levels to consider using biopigments as a vehicle to introduce the scientific method to their students. To facilitate the implementation of biopigments into science and art curricula, we have provided a list of useful online resources and information about procuring materials [...] as well as recommend ways to evaluate the effectiveness of the lesson [...]."

Original article (and image source):
Charkoudian LK, Fitzgerald JT, Khosla C, Champlin A (2010) In Living Color: Bacterial Pigments as an Untapped Resource in the Classroom and Beyond. PLoS Biol 8(10): e1000510. doi:10.1371/journal.pbio.1000510
Image: “Elvis Lives!” painted on agar media plates using the bacterium Streptomyces coelicolor.



Related links:
- Microbial Art, a collection of unique artworks created using living bacteria, fungi, and protists.
- Painting With Penicillin: Alexander Fleming's Germ Art. The scientist created works of art using microbes, but did his artwork help lead him to his greatest discovery? By Rob Dunn. Smithsonian.com, July 12, 2010.
- Streptomyces: they're twisted! Twisted Bacteria, Aug 10, 2007.

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A new way to make polyketides

Polyketides are a class of natural products isolated from microbes, plants and invertebrates which includes an impressive number of clinically effective drugs with diverse activities. To name a few examples: erythromycin (antibiotic), rapamycin (immunosuppressive), amphotericin (antifungal), avermectin (antiparasitic), and doxorubicin (anticancer). As other natural products do, polyketides may play disparate roles in the producing organisms, from defensive weapons (inhibiting growth of competitors, or acting against predators) to signaling molecules (working as messengers between social organisms). In Mycobacterium tuberculosis, some polyketides are key intermediates in the synthesis of complex lipids. These lipids are important components of the unusually thick cell envelope, and help the microbe to be a successful pathogen. Therefore, the study of polyketide synthesis in this bacterium may lead to the design of specific inhibitors as new anti-mycobacterial drugs.

Polyketides are produced through a stepwise condensation of simple carboxylic acid precursors, resembling fatty acid biosythesis. This task is performed by enzymes known as polyketide synthases (PKSs). There are several types of PKSs, from relatively simple proteins to large multienzymatic complexes possessing tens of catalytic sites. They use any of two general mechanisms: (1) modular — in which each set of catalytic sites is used only once during the biosynthetic process, and (2) iterative — in which the same set of active sites is used repeatedly. This week in PLoS Biology, Rajesh Gokhale and colleagues present their research involving a peculiar PKS from M. tuberculosis. The PKS12 protein is encoded by the largest gene in the microbe's genome, and participates in the synthesis of an antigenic phosphoglycolipid. Most remarkably, this PKS appears to use a new hybrid "modularly iterative" mechanism for polyketide synthesis. Several molecules of the PKS12 protein join together to form a supramolecular assembly, which performs repetitive cycles of iterations. The protein assembly is formed by specific intermolecular interactions between N- and C-terminus linkers. This study provides another example of the catalytic and mechanistic versatility of PKSs — natural product biosynthesis is an inexhaustible source for new biochemistry!

Citation (open access):
Chopra T, Banerjee S, Gupta S, Yadav G, Anand S, Surolia A, Roy RP, Mohanty D, Gokhale RS (2008). Novel intermolecular iterative mechanism for biosynthesis of mycoketide catalyzed by a bimodular polyketide synthase. PLoS Biology 6(7), e163. DOI: 10.1371/journal.pbio.0060163

Image: model of the PKS12 protein, modified from Figure 5 of the cited article.


Related links:

• Cracking the Polyketide Code. PLoS Biology (2004) 2(2): e35.
• Polyketide Biosynthesis: The Erythromycin Example (video of an excellent talk by Chaitan Khosla, May 2007). iBioSeminars, American Society for Cell Biology. The first part of the talk (Polyketides and Polyketide Biosynthesis) is also available at Google Video, and is embedded below.

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Combinatorial biosynthesis, but not as we know it

Combinatorial biosynthesis can be understood as a special case of metabolic engineering, where genes responsible for individual metabolic reactions from different organisms are combined to generate hybrid metabolic pathways. An ideal result consists of a genetically-modified organism (or a collection of such microorganisms) that is useful for in vivo production of novel compounds. Nevertheless, there are examples of in vitro combinatorial biosynthesis (*), such as glycorandomization (a biocatalytic technique that uses purified enzymes to activate and attach sugars to natural products).

One step beyond, a recent report in ACS Chemical Biology describes a new in vitro approach for the generation of combinatorial libraries of compounds derived from natural products. As a proof of concept, the authors combined three type-III polyketide synthases (PKSs), 16 different precursors (acyl-CoA esters) and three post-PKS tailoring enzymes. Remarkably, this strategy was adapted to a convenient microarray format (30-nanoliter reactions), to enable high-throughput synthesis. Even better, the same microarray slide was used to screen for bioactivity of the synthesized products, through an assay for inhibition of human protein kinase FynT. This approach is, therefore, potentially useful for the identification of new non-natural compounds displaying biological activities.

Reference: Kwon SJ, Lee My, Ku B, Sherman DH, Dordick JS.
High-throughput, microarray-based synthesis of natural product analogues via in vitro metabolic pathway construction.
ACS Chem. Biol. 2007 May 25 (ASAP Article). PubMed link.

[(*) I understand that some people may prefer to keep the term "combinatorial biosynthesis" only for in vivo approaches. Perhaps they're right, but I view biocatalysis (in vitro utilization of purified enzymes for chemical transformations) as a special type of biosynthesis.]

[Another note: I'm not a Star-Trek fan, but I think that the line "It's life, Jim, but not as we know it" was told by the Doc to the captain on seeing new life on a strange planet. However, I didn't learn the line directly from Star Trek, but from an article titled "Life, Jim, but not as we know it"? Transmissible dementias and the prion protein, Br. J. Psychiatry (1991) 158: 457-4710, authored by PJ Harrison & GW Roberts. I got to know this article while learning about neurodegenerative diseases during my M.S. studies (uf, feels like late Pleistocene). It was such a great title for a story on prions, it just stuck in my mind.]

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