# Convergent Evolution in Natural Product Biosynthesis

> **NIH NIH R35** · UNIVERSITY OF GEORGIA · 2024 · $357,125

## Abstract

Abstract
Natural products are non-essential small organic molecules produced by living organisms, such as bacteria,
fungi, plants, and animals. They have been described as the most important structural leads within the
pharmaceutical industry, and current estimates suggest that 50–70% of medicines can be traced back to a
natural product origin, including more than 60% of the anticancer drugs brought to market in the last 25 years.
One of the first major hurdles in any drug development program involves an initial “hit identification”, a process
commonly accomplished through large-scale screening programs. Consequently, establishing a new natural
product-driven approach to drug-lead identification has the potential to markedly improve the efficiency of the
drug development process. To this end, herein we introduce a new strategy that attempts to shift the burden of
hit identification from Scientist to Nature. Specifically, we propose that instances of “convergent evolution” in
natural product biosynthesis may be a marker for molecules of significant biological importance given they have
survived the natural selection process on more than one occasion. Selection of our targets, the halenaquinones,
viridins, wortmannins, and hibiscones, was guided by a combination of biosynthetic considerations and
preestablished anticancer activities. We have already developed an innovative and scalable route to many of
halenaquinone family members. Our approach takes advantage of the inherent reactivity present within these
molecules, and when considered alongside the simple nature of the reagents employed and the structure of the
various coisolates, we believe this to be in support of our biosynthetic speculation. We have already
demonstrated our approach is directly applicable to the synthesis of simplified analogues, and we envision it will
translate to our remaining natural product families. The first exhaustive SAR studies, done in combination with
computational and experimental docking studies, will inform the development of new anti-cancer drug leads and
simplified chemical probes. In the long-term, it is envisioned instances of “convergent evolution” in natural
product biosynthesis may develop in to a general approach to drug discovery.

## Key facts

- **NIH application ID:** 10941818
- **Project number:** 1R35GM155161-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Christopher Newton
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $357,125
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941818

## Citation

> US National Institutes of Health, RePORTER application 10941818, Convergent Evolution in Natural Product Biosynthesis (1R35GM155161-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10941818. Licensed CC0.

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