# Developing Methanosarcina spp. as a model system to study cytochromes c and their role in archaeal methane metabolism

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $69,500

## Abstract

Project Summary/Abstract
Cytochromes c are crucial in methane-metabolizing archaea for the production and consumption of methane
coupled to growth and energy conservation. Overall, methane-metabolizing archaea mediate the net flux of
methane released into the atmosphere and thus, significantly impact the global methane cycle and climate
change. Based on genomic studies, Cytochromes c have been hypothesized to play an important role in
methane metabolism however the underlying molecular mechanisms remain elusive, primarily due to the
absence of a well-developed genetic model system. Even attempts to study archaeal cytochrome c using an
alternative approach such as heterologous expression in well-established bacterial systems have not proven
successful so far. The main focus of the proposed research is to develop a genetically tractable methanogenic
archaeon, Methanosarcina acetivorans, as a platform to functionally characterize archaeal cytochrome c and
gain physiological insights into the role of cytochrome c in methane metabolism across different archaeal
species.
Cytochromes c are ubiquitous electron transfer proteins that require a covalent attachment to its heme co-factor,
a process called cytochrome c biogenesis. Coordination between the cytochrome c biogenesis pathway and the
cytochrome c of interest is critical for the successful production of a functional cytochrome c in a heterologous
host. Using genetic and biochemical tools, I have recently characterized the cytochrome c biogenesis pathway
in the model methanogenic archaeon, Methanosarcina acetivorans. Using this knowledge, the project aims to
develop M. acetivorans as a genetic chassis to produce and functionally characterize archaeal cytochrome c
from diverse archaeal species. Aim1 of the project will functionally characterize the crucial
cytochromes c belonging to methane-producing archaea or methanogens, and Aim2 will study these proteins
from methane-consuming archaea using both in vitro and in vivo analyses. This research will improve our
understanding of methane metabolism and lead to the development of an archaeal host to study cytochrome c
proteins from archaea. Ultimately, the knowledge garnered from these studies can be used to develop
sustainable solutions for the global climate crisis and mitigate its harmful impacts on human health.

## Key facts

- **NIH application ID:** 10679362
- **Project number:** 1F32GM150233-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Dinesh Gupta
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $69,500
- **Award type:** 1
- **Project period:** 2023-09-30 → 2025-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679362

## Citation

> US National Institutes of Health, RePORTER application 10679362, Developing Methanosarcina spp. as a model system to study cytochromes c and their role in archaeal methane metabolism (1F32GM150233-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10679362. Licensed CC0.

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