Astaxanthin

Metabolic engineering

The cost of astaxanthin production, high commercial price and lack of a leading fermentation production systems, combined with the shortfalls of chemical synthesis mean that research into alternative fermentation production methods has been carried out. Metabolic engineering offers the opportunity to create biological systems for the production of a specific target compound. The metabolic engineering of bacteria (Escherichia coli) recently allowed production of astaxanthin at >90% of the total carotenoids, providing the first engineered production system capable of efficient astaxanthin production. Astaxanthin biosynthesis proceeds from beta-carotene via either zeaxanthin or canthaxanthin. Historically, it has been assumed that astaxanthin biosynthesis proceeds along both routes. However, recent work has suggested that efficient biosynthesis may, in fact, proceed from beta-carotene to astaxanthin via zeaxanthin. The production of astaxanthin by metabolic engineering, in isolation, will not provide a suitable alternative to current commercial methods. Rather, a bioprocess approach should be adopted. Such an approach would consider fermentation conditions and economics, as well as downstream processing (extraction). Carotenoid extraction has been studied extensively, for example, the extraction of canthaxanthin (a precursor to astaxanthin) was studied within an E. coli production process demonstrating that extraction efficiency was increased substantially when two solvents, acetone and methanol, were used sequentially rather than as a combined solution.

Difference between natural and synthetic forms

Astaxanthin has two chiral centers, at the 3- and 3′-positions. Therefore, there are three stereoisomers; (3R,3′R), (3R,3′S) (meso), and (3S,3′S). Synthetic astaxanthin contains a mixture of the three, in approximately 1:2:1 proportions. Naturally occurring astaxanthin varies considerably from one organism to another. The astaxanthin in fish is of whatever stereoisomer the fish ingested. The astaxanthin produced by Haematococcus pluvialis, which is commonly used in the feed of animals that are in turn consumed by humans, is the (3S,3′S) stereoisomer.

Uses

Astaxanthin is used as a feed supplement for salmon, crabs, shrimp, chickens and egg production.

For seafood and animals

The primary use of synthetic astaxanthin today is as an animal feed additive to impart coloration, including farm-raised salmon and egg yolks. Synthetic carotenoid pigments colored yellow, red or orange represent about 15–25% of the cost of production of commercial salmon feed. Today, almost all commercial astaxanthin for aquaculture is produced synthetically from petrochemical sources. While it constitutes a tiny portion of salmon feed (50 to 100 parts per million), astaxanthin represents a major share of the cost, up to 20%.

Class action lawsuits have been filed against some major grocery store chains for not clearly labeling the salmon "color added". The chains followed up quickly by labeling all such salmon as "color added". "...law-firm Smith & Lowney persisted with the suit for damages, but a Seattle judge dismissed [the case], ruling that enforcement of the applicable food laws was up to government and not individuals."

For humans

The primary use for humans is as a dietary supplement. Research suggests that, due to astaxanthin's antioxidant activity, it may be beneficial in cardiovascular, immune, inflammatory and neurodegenerative diseases. Some research supports the assumption that it may protect body tissues from oxidative and ultraviolet damage through its suppression of NF-κB activation.

A 2015 meta-analysis of data from ten randomized, controlled trial groups in seven published clinical trials, doses ranging 4 to 20 mg/day, did not indicate a significant effect of supplementation with astaxanthin on plasma lipids profile or fasting glucose.

Role in the food chain

It has been speculated that gulls are "flushed" pink when molting, especially in areas with farm-raised salmon. However, not enough is known about the relationship between astaxanthin and plumage. For example, cardinals seem to produce astaxanthin from carotenoids when molting, even when fed primarily seed with natural yellow dye.

Lobsters, shrimp, and some crabs turn red when cooked because the astaxanthin, which was bound to the protein in the shell, becomes free as the protein denatures and unwinds. The freed pigment is thus available to absorb light and produce the red color.

Regulations

In April 2009, the United States Food and Drug Administration approved astaxanthin as an additive for fish feed only as a component of a stabilized color additive mixture. Color additive mixtures for fish feed made with astaxanthin may contain only those diluents that are suitable. The color additives astaxanthin, ultramarine blue, canthaxanthin, synthetic iron oxide, dried algae meal, Tagetes meal and extract, and corn endosperm oil are approved for specific uses in animal foods. Haematococcus algae meal (21 CFR 73.185) and Phaffia yeast (21 CFR 73.355) for use in fish feed to color salmonoids were added in 2000. In the European Union, astaxanthin-containing food supplements derived from sources that have no history of use as a source of food in Europe, fall under the remit of the Novel Food legislation, EC (No.) 258/97. Since 1997, there have been five novel food applications concerning products that contain astaxanthin extracted from these novel sources. In each case, these applications have been simplified or substantial equivalence applications, because astaxanthin is recognised as a food component in the EU diet.