# Investigating (di)terpenoid biosynthesis

> **NIH NIH R35** · IOWA STATE UNIVERSITY · 2021 · $537,153

## Abstract

Natural products have a proven record of providing a significant fraction, either directly or as lead
compounds, of human medicines. Among natural products, the terpenoids (isoprenoids) stand out as
being the largest class (>50,000 already known), with the 20-carbon diterpenoids targeted here forming a
significant fraction of these (>12,000 known). The extensive diversification of diterpenoids indicates that
the manifold hydrocarbon skeletons that can be formed from this C20 backbone, particularly the decalin
core ring structure found in the labdane-related diterpenoids (>7,000 known), provide privileged scaffolds
for derivation of biological activity. Indeed, a number of these labdane-related diterpenoids are used as
pharmaceuticals (e.g., the antibiotic mutilins) or are being investigated for such use (e.g., the
tanshinones, triptolide, andrographolide, etc.). In addition, we have contributed to the discovery that the
human pathogen Mycobacterium tuberculosis utilizes labdane-related diterpenoid metabolism in
construction of an immune-modulatory factor. Accordingly, we propose here to continue our productive
studies of the biosynthetic enzymes required to produce bioactive diterpenoids. Specifically, we will build
on our previous work in this area, which includes investigations of enzymatic structure-function that have
provided novel biosynthetic access to an array of diterpenoids, as well as elucidation of strategically
selected diterpenoid metabolic networks. This MIRA proposal covers our systematic studies in this area,
advancing our long-term goal of engineering enzymes and metabolic pathways for the production of
targeted libraries and specific individual terpenoid ‘natural’ products, which are being already using for
investigation of pharmaceutical utility.

## Key facts

- **NIH application ID:** 10171598
- **Project number:** 5R35GM131885-03
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** REUBEN JOHN PETERS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $537,153
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171598

## Citation

> US National Institutes of Health, RePORTER application 10171598, Investigating (di)terpenoid biosynthesis (5R35GM131885-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10171598. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*