Type: INT 97-11 NSF/Tokyo Report: New Frontiers in Microbiology

Exposure: Public NSF

Org: INT

Date: 3/24/97

Replaces: None

The National Science Foundation\'s offices in Tokyo and in Paris
periodically report on developments abroad that are related to the
Foundation\'s mission. These documents present facts for the use of NSF
program managers and policy makers; they are not statements of NSF
policy.

Special Scientific Report #97-06 (February 28, 1997)

The following report was prepared by Dr. Machi F. Dilworth, Program
Director, Division of Integrative Biology and Neurosciences at NSF. In
November 1996, Dr. Dilworth began a 10- month fellowship at the
Laboratory for Regulation of Plant Functions, Institute of Physical and
Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-01, Japan. At
RIKEN, Dr. Dilworth is working jointly with Dr. Shigeo Yoshida. Dr.
Dilworth received an Science and Technology Agency (STA) Fellowship to
partially support her visit to Japan. Dr. Dilworth can be reached via
email at: mdilwort@nsf.gov OR mdilwort@postman.riken.go.jp

**The 5th Japan Science and Technology Corporation International
Symposium: New Frontiers in Microbiology**

January 30-31, 1997, Tokyo, Japan

Meeting Report

This symposium was organized under the auspices of the Japan Science and
Technology Corporation (JST) with Dr. Koki Horikoshi as the chair of the
organizing committee. The organizing committee consisted of 7
microbiologists including Dr. Roy Doi of UC Davis and Dr. James Tiedje
of Michigan State University. JST is a semi-governmental organization
associated with the Science and Technology Agency (STA) and it
administers primarily extramural research activities of STA.

The stated objectives of the symposium were to highlight and emphasize
the importance of microbiology in our lives, and to provide a forum for
stimulating discussions among researchers working at the forefront of
microbiology research from different perspectives using a variety of
approaches. Although not mentioned in its English version, the Japanese
version of the symposium scope statement included the following
sentences (my translation): \"With rapid advances in scientific methods
and technologies such as genetic engineering and PCR, microbiology is
now entering into a new era. It is an opportune moment for Japan to take
the initiative in leading new frontiers in microbiology.\"

The symposium was well attended with 450 pre-registered participants and
additional 30-40 on-site registrants. They appeared to represent
academia, government labs, and the industry fairly evenly. I noted
French and US Embassy representatives among the audience.

New frontiers (or new opportunity areas) in microbiology identified by
some of the speakers are:

\* Signal transduction mechanisms by which microorganisms perceive and
respond to their environment

\* An interface between genetics and bio-organic chemistry

\* An interface between microbiology and soil chemistry

\* Exploiting the genome sequence information to gain misnderstanding of
the biology of microbes

\* Application of thermozymes and other unique properties of microbes

Areas frequently mentioned as in need of more research are:

\* Microbial physiology

\* Basic investigation of enzymology, metabolic regulation and role of
secondary metabolites

In his closing remarks, Dr. Koki Horikoshi stressed the resiliency of
microbes by quoting his mentor, Dr. Kinichiro

Sakaguchi, \"Microorganisms will give you anything you want if you know
how to ask them.\" He stated his belief that by selecting the right
organism, any desired product can be obtained given the diversity of
microorganisms available. He also stated that the organisms that are
considered difficult-to-culture can be changed to the readily-culturable
organisms by finding the right culture conditions; and even the
organisms that are considered unculturable can be cultured if the right
conditions can be provided.

He announced that an international extremophile meeting will be held in
Yokohama in January of 1998 and the first circular will be issued in
February of 1997. One of the main foci of the meeting will be industrial
application of extremophiles.

Scientific highlights (some of the talks that I found interesting):

Koki Horikoshi (Tokyo University) gave a brief report on the microbial
cultures collected from a depth of 11,000 m in the latest expedition to
the Mariana Trench. Found among the collection are alkaliphiles,
barophiles, thermophiles, psychrophiles, halophiles, acidophiles, and a
relatively high amount of non-extremophiles some of which are amylase
and protease producers. He found the presence of non extremophiles
particularly interesting. Other unexpected findings included
alkaliphiles that can grow well at pH 7.0, and thermophiles that can
grow well at 4C.

James A. Hoch (the Scripps Research Institute) talked about his studies
on the mechanisms of sporulation of Bacillus subtilis with a focus on
the phosphorelay signal transduction system. He is looking at a
multicomponent phosphorelay system in operation during sporulation as a
signal integration circuit. His study indicates that microbes have
signal transduction systems as complex as eukaryotes.

Terry Ann Krulwich (Mount Sinai School of Medicine) presented her
studies of extremely alkaliphilic Bacillus strains to determine what
gene products and what physiological processes are responsible for the
alkaliphilic characteristics. Her multifaceted studies involve the
analysis of ion and proton transport across cell membranes, and the
characterization of the structure of proteins (both membrane proteins
and enzymes) that are exposed to high pH.

Gerald Fink (Whitehead Institute for Biomedical Research) made a point
that the genome sequence information is invaluable because it tells us
what we did not know about the organisms. He then proceeded to pose the
question, \"how many genomes do we need to sequence to know what makes a
fungus a fungus?\" His conclusion was that an algorithm needs to be
developed to answer this question, and that understanding of the
developmental pathway in the fungus will provide a base-line information
necessary for developing such an algorithm.

David A. Hopwood (John Innes Center, U.K.) described how recent advances
in gene identification have led to a complete understanding of the
biosynthetic pathway of polyketide (PKS) antibiotics in Streptomyces and
how it, in turn, has led to the production of novel products in
microbes. Using the knowledge gained from detailed enzymological and
protein structural studies of PKS synthesis enzymes and the PKS genes
isolated from Streptomyces, Dr. Hopwood is engineering a new
Streptomyces strain that produces a novel metabolite through a
combination of several PKS genes.

Arnold L. Demain (MIT) gave an overview of the environmental regulation
of secondary metabolite production at the molecular level. The synthesis
of secondary metabolism is often coded by clustered genes on chromosomal
DNA and infrequently on plasmid DNA. As the main functions of secondary
metabolism in nature is to allow the organism to survive, the genes of
secondary metabolism are not expressed under conditions supporting the
maximum growth rate. The environmental factors regulate the expression
of genes for secondary metabolism. Therefore, the environment of the
industrial microorganism in the fermentation factory is of crucial
importance to industry in order to achieve the most efficient production
of the desired secondary metabolite.

Kenneth N. Timmis (GBF National Research Center for Biotechnology,
Germany) presented his work on engineering of microorganisms with novel
catabolic properties designed for uses in bioremediation. He emphasized
the importance of understanding the chemical and physical interaction
between the soil particles and the target molecules because it
determines bioavailability of the target molecule. As an example, he has
found that treating the PCB containing soil with a surfactant increase
the amount of PCB available for microbial degradation in the soil. Based
on that finding, he genetically designed a microorganism that can
secrete a surfactant and can remove PCB efficiently from the soil.

Yoshiharu Doi (the Institute of Physical and Chemical Research /RIKEN,
Japan) has found microbes that synthesize a variety of new polyesters.
For example, Aeromonas caviae produces a random co-polymer (PHA) of
3-hydroxybutyurate (3HB) and 3- hydroxyhexanoate (3HH) under aerobic
conditions. Dr. Doi has cloned the genes involved in the co-polymer
synthesis, and, by manipulating the gene expression and the nutrient
conditions, he succeeded in making the microbe produce PHA up to 90% of
its dry weight. A parallel study in developing an organism that can
efficiently degrade PHA is being carried out. He is also developing
E.coli strain that can produce poly (3HB) of extremely high molecular
weight (up to 20 M 3HB units) from glucose.