How to find microbes that make Gold.

The production of microbial products is a huge global industry with many billions of dollars of products sold world wide that are originally derived from microbes. There is much scope to add new bioproducts to that list.

It requires innovative thinking, a good bioproduct discovery strategy, and alertness to opportunities that you might come across while you are reading about biology, science, and business.

Remember, during your searches for bioproduct candidates, the success of French microbiologist Louis Pasteur, who is famous for observing that fortune favours the prepared mind.

Some general approaches and ideas for discovery of novel bioactive compounds from microbes are:

1. Tap into microbial biodiversity
   
2. Search for novel organisms
3. Be alert to microbial culture and enrichment concepts. These include using indicator agar plates, for example containing enzyme substrates that change colour during a reaction.
4. Search in novel or extreme microbial environments.
5. Find and grow previously unculturable organisms.
6. Find compounds through gene cloning (metagenomics) from organisms that cannot be grown. see eg How to Find New Antibiotics, Jo Handelsman, The Scientist Volume 19 | Issue 19 | Page 20 | Oct. 10, 2005
   
7. Exploit suitable assays or screens to find novel biological activities. eg Coloured compounds produced by microbial colonies are easier to find than colourless compounds. Similarly substrates that produce colour (chromogenic compounds) or fluorescence (fluorogenic compounds) by a chemical reaction are extremly useful if a relevant or practically useful way of exploiting a reaction can be devised.
   
8. It's possible to find a novel microbe to make or provide a useful biological activity previously unknown in microbes using a well chosen assay.
9. Exploit specific or sensitive assay approaches.
10. Possibly identify a novel "drug" target to help develop an assay.
11. Use a high through-put assay or screening approach ( eg screens of millions of colonies on plates, screens in microtitre dishes).
12. Screen pools of different compounds or microbes in the one assay to find which pool has the posive microbe.
13. Use of chemical analysis techniques such as Mass spectroscopy, in innovative ways to allow high through-put detection on novel molecules
14. Encapsulate individual cells or samples in polmeric microscopic beads to facilitate screening
    

Pundit is going to add useful hyper links to this list to expand this information.

But why not help the Pundit and put your questions and comments about them below so we can discover good ideas by dialog.

For example, answer this question I'm putting forward to start you thinking about useful approaches:

How are sensitive and specific assays helpful to the bioproduct discovery process, and can you think of particular opportunities they open up?

There is plenty of helpful general reading that can help you prepare for the task of exploiting microbial novelty:

• Pages 26- 32 of The textbook Microbial Biotechnology by A.N. Glazer and H. Nikado, Freeman, 1995 are a good short introduction to some previously discovered microbial bioproducts such as plastics and drugs.
• Chapter 15. of Microbe, M. Schaechter et al ASM Press 2006 is very good background reading about bacterial diversity.
• Several previous posts at this site deal with compounds, such as siderophores, that are produced by soil streptomycete bacteria (these posts are readily accessible via the index hyper-link in the side-bar on the right.)
  

Microbe. The World of Microbes.

Epulopiscium fishelsoni

As a start to this discussion forum, it's good to go to the website devoted to book Microbe that inspired this weblog. This website is here.

We are starting discussions with chapter 1 of this book- The World of Microbes.

Let's get started by posting a study question for discussion in the comments thread.

Question
Bacteria range in volume over a million-fold. Discuss some of the consequences of being larger or smaller than average?

Update of question and posting with more information to assist students. 4th March 2007
Here is some extra information that can assist students understand how size has implications for available membrane surface area to service the metabolic requirement of a unit cell volume.

To understand the point of the question about size, students need to think about have the ration of surface are:cell volume changes with increase in size. SA/Vol Ratio~diameter squared/diameter cubed~inversely proportional to diameter, with similar cell shapes.

To see some consequencences raised by the biology of large bacteria you need to read about observations that have been made on Epulopiscium bacteria, usually called epulos. The paper by K D Clements and S Bullivant (1991) An unusual symbiont from the gut of surgeonfishes may be the largest known prokaryote. J Bacteriol. 1991 September; 173(17): 5359–5362 provides some good interesting insights.

Figure 1 of this paper shows how large epulos are.
J Bacteriol. 1991 September; 173(17): 5359–5362. Figure 1. Light micrograph of an Epulo. The letter C indicates a smaller, eukaryotic ciliate.

J Bacteriol. 1991 September; 173(17): 5359–5362. Figure 3. Electron micrograph of a thin section of an Epulopiscium bacterium showing concolutions to cytoplasmic membrane. Such convolutions would increase the membrane area to cell volume ratio of these large bacteria

Thus epulos have a peripheral layer of highly convoluted cytoplasmic membrane - which has been interpreted as a mechanism increase in membrane area to compensate for some surface area to volume related challenges that they face because of their large size.

Extra reading for the high achieving student:
In the links at the Microbe Chapter 1 webpage, this is worth studying several times in the course.