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Title: INT 97-11  NSF/Tokyo Report: New Frontiers in Microbiology
Date:  March 24, 1997



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.