An efficient process to rapidly discover new
"enediyne natural products" from soil microbes has been developed by scientists from the Florida campus of The Scripps Research Institute
(TSRI). This could be further
developed into extremely potent anticancer drugs.
The study highlights microbial natural products as abundant sources
of new drug leads. The researchers' discovery process involves
prioritizing the microbes from the TSRI strain collection and focusing
on the ones that are genetically predisposed to produce specific
families of natural products. The scientists say this process saves time
and resources in comparison to the traditional approaches used to
identify these rare molecules.
‘A new family of enediyne natural products, called tiancimycins, (TNMs) kills selected cancer cells more rapidly and completely in comparison to toxic molecules used in FDA-approved antibody-drug conjugates (ADCs).’
The study, led by TSRI Professor Ben Shen, was published in the journal mBio
Shen and his colleagues uncovered a new family of enediyne natural
products, called tiancimycins, (TNMs) which kill selected cancer cells
more rapidly and completely in comparison to toxic molecules used in
FDA-approved antibody-drug conjugates (ADCs)- monoclonal antibodies
attached to cytotoxic drugs that target only cancer cells.
The scientists also discovered several new producers of C-1027, an
antitumor antibiotic currently in clinical development, which can
produce C-1027 at much higher levels.
It has been more than a decade since Shen first reported on the
C-1027 enediyne biosynthetic machinery, and he speculated then that the
knowledge obtained from studying biosynthesis of C-1027, and other
enediynes, could be used for the discovery of novel enediyne natural
"The enediynes represent one of the most fascinating families of
natural products for their extraordinary biological activities," Shen
said. "By surveying 3,400 strains from the TSRI collection, we were able
to identify 81 strains that harbor genes encoding enediynes. With what
we know, we can predict novel structural insights that can be exploited
to radically accelerate enediyne-based drug discovery and development."
"The work described by the Shen group is an excellent example of
what can be achieved by coupling state of the art genomic analyses of
potential biosynthetic clusters and modern physicochemical techniques,"
said David J. Newman, retired chief of the National Cancer Institute's
Natural Products Branch. "As a result of their work, the potential
number of enediynes has significantly increased."
Shen's method of strain prioritization and genome mining means a far
more efficient use of resources involved in the discovery process,
targeting only those strains that look to produce the most important
"This study shows that the potential to rapidly discover new
enediyne natural products from a large strain collection is within our
reach," said TSRI Research Associate Xiaohui Yan, one of four first
authors of the study. "We also show the feasibility of manipulating
tiancimycin biosynthesis in vivo, which means that sufficient quantities
of these precious natural products can be reliably produced by
microbial fermentation for drug development and eventual