This document summarizes research into stimulating the production of the antibiotic platensimycin by the actinomycete Streptomyces platensis. Certain vitamins and inorganic salts were found to increase platensimycin yields when added to the production medium, including calcium pantothenate, riboflavin, and potassium chloride. Calcium pantothenate and riboflavin are involved as precursors in the biosynthetic pathway of platensimycin. The goal of the work is to better understand the precursors and regulators of platensimycin production to aid future commercial production. Future work will examine the effects of purines, pyrimidines, and positive compounds on a high

1. Gulaba Khan, Victoria Korn, Amreen Patel, and Klarissa Jones
Drew University/ RISE
Stimulation of Platensimycin Production by Inorganic Salts
and Vitamins
BACKGROUND
In the early 1900’s, infectious diseases were
the leading cause of death in the world. It
wasn’t until 1928 that the first medically
useful antibiotic, penicillin, was
discovered. Antibiotic discovery declined
after 1970 within the pharmaceutical
industry and infectious diseases started to
develop resistance to antibiotics. In 2005,
Merck scientists found that the
actinomycete Streptomyces
platensis produced platensimycin, an
antibiotic that inhibits the fatty acid
synthesis II (FASII) pathway in prokaryotes.
Humans only utilize the FASI pathway,
making platensimycin nontoxic to human
beings. Platensimycin has also been found
to be active against resistant pathogens
(including MRSA, VRE, and
Mycobacterium tuberculosis). It also is
active against diabetes.
RESULTS OF THIS YEAR
We continued to study the effects of primary
metabolites, specifically vitamins, on the
production of platensimycin. Of the vitamins
tested, calcium pantothenate and riboflavin
were stimulatory. Calcium pantothenate is
stimulatory because it is a precursor of
Coenzyme A, which is involved as an
activator of several steps in the
platensimycin biosynthetic scheme.
Riboflavin is stimulatory because it is a
precursor of the flavins, FMN and FAD. Two
of the enzymes of platensimycin
biosynthesis are flavin-dependent.
PREVIOUS WORK
Our laboratory group successfully
developed a chemically-defined production
medium (PM7A) that is able to support
antibiotic production by S. platensis. It
contains lactose, glucose, MOPS buffer,
ammonium sulfate at pH 7. In the recent
past, our group has been testing primary
metabolites as possible stimulators of
platensimycin production in this medium. Of
eighteen amino acids tested, only aspartic
acid showed activity.
METHODS
We test for antibiotic production up to 14
days using bioassays. Samples of the
production flasks are removed and paper
disks are dipped into these samples. These
disks are placed on agar plates inoculated
with Staphylococcus aureus. We incubate
these plates at 25-27 degrees overnight and
the next day we observe them and measure
the diameters of clear zones of inhibition
around the disks.
CONCLUSIONS
Examination of the knowledge of
platensimycin biosynthesis offers some
reasons for the activity of our stimulatory
compounds. Specifically, riboflavin is
involved in the biosynthetic pathway.
Pantothenic Acid was seen to have
stimulatory properties as indicated by Figure
1. As demonstrated by the Figure 2, KCl
stimulates antibiotic production. Riboflavin
was also stimulatory as seen as figure 3.
Riboflavin is stimulatory because it is a
precursor of the flavins, FMN and FAD,
which are involved in platensimycin
biosynthesis.
ACKNOWLEDGEMENTS
Special thanks to Dr. A. L Demain, Dr. J
Kettenring, Mira Patel, RISE, DSSI, and
Dr. B Shen of Scripps Institute, Florida.
platensimycin
GOAL OF OUR WORK
Through our work, we hope to learn about
the precursors and/or regulators of the
pathway involved in the production of
platensimycin. Our work is also significant
for future production of this antibiotic, where
information about compounds that stimulate
production could be very useful for
commercial production.
FUTURE WORK
● Determine the effects of purines and
pyrimidines on platensimycin
biosynthesis.
● Determine effects of positive compounds
on a high-producing mutant of
Streptomyces platensis.
Stimulation by Pantothenic Acid
PM7A
100X Pantothenic Acid+ PM7A
1000X Pantothenic Acid+ PM7A
Stimulation by KCl
KCl+ PM7A
PM7A
Stimulation by Riboflavin
Riboflavin + PM7A
PM7A
Figure 1
Figure 3
Figure 2