You are here

Microbial biosynthesis of opioid antagonists a novel low cost method for producing addiction pharmacotherapies

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DA044069-01
Agency Tracking Number: R43DA044069
Amount: $225,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIDA
Solicitation Number: PA16-302
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-04-01
Award End Date (Contract End Date): 2019-03-31
Small Business Information
2627 HANOVER ST
Palo Alto, CA 94304-1118
United States
DUNS: 078843373
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 KRISTY HAWKINS
 (510) 450-0761
 contact@amyris.com
Business Contact
 CATHERINE (KATE) THODEY
Phone: (650) 799-2851
Email: kate.thodey@gmail.com
Research Institution
N/A
Abstract

Abstract
Medicinal opioids are essential medicines for treating pain but exhibit addictive properties The United
States has committed significant resources to curb opioid dependence and overdose The nal opioids a suite
of antagonist and mixed partial agonist opioids are an important group of pharmacotherapies used in drug
addicted patients for treating overdose managing symptoms during detoxification and maintenance by
blocking reward responses In pain management patients nal opioids are used in combination with opioids to
prevent addiction and abuse and to reduce side effects
Current production methods for nal opioids are inefficient expensive and rely on the farming of a drug
crop The raw starting materials for nal opioid synthesis are natural opiates that are extracted from opium
poppy and subsequently chemically modified through a series of inefficient reaction steps As a result of the
costs associated with this process nal opioids command a substantially higher price than opiates that have not
been chemically modified For example natural morphine active pharmaceutical ingredient API retails for
$ kg whereas naloxone and buprenorphine cost $ kg and $ kg respectively
Antheia s technology will produce nal opioids efficiently and at a fraction of the cost of the current
production methods The novel technology allows for total biosynthesis of nal opioids by yeast fermentation
thereby removing the reliance on drug crop farming and changing the way these life saving therapeutics are
manufactured Antheia will leverage its existing technology for producing opioids in yeast and extend the
biosynthetic capabilities of these strains to include precursors of the nal opioids and ultimately the end
products naloxone naltrexone and buprenorphine Technoeconomic models indicate that Antheia s unique
technology will result in greater than a fold reduction in the cost of producing these compounds
The objective of this Phase I SBIR project will be to develop engineered yeast strains that produce high
levels of noroxymorphone the direct precursor for the nal opioids naloxone and naltrexone through whole cell
biocatalysis First a yeast strain capable of high level oxycodone biosynthesis will be constructed by the
addition and optimization of two enzymatic steps to Antheia s existing opioid production strains Second two
novel O demethylase and N demethylase enzyme activities will be developed with enzyme evolution and a
high throughput colorimetric screening assay Finally the O and N demethylase activities will be combined
with the optimized oxycodone producing strain to deliver a novel bioproduction system for noroxymorphone
This project will address major technical barriers to the microbial production of nal opioids and support the
commercial viability of this technology By addressing much of the technical risk this SBIR project will enable
investor funded development and scale up and Antheia s entry into a new product line to help combat growing
opioid abuse and addiction Narrative
Nal opioids such as naloxone naltrexone and buprenorphine are pharmacotherapies that save
and rebuild lives by treating chemical dependence on opioids However these active
pharmaceutical ingredients demand a premium price due to their complex production process in
which molecules extracted from opium poppy are tailored to exhibit antagonist properties
Antheia s unique microbial production technology will dramatically decrease the price of
producing nal opioids and provide a secure sustained supply for drug addiction treatment

* Information listed above is at the time of submission. *

US Flag An Official Website of the United States Government