Shikimic Acid Fermentation

In the Name of God

Biotechnology MSc. Seminar:

Current issues in production of Shikimic Acid, intermediate for the production of Oseltamivir, the Avian Flu drug

Supervised by:

Dr. Reza Yegani

Dr. Mohammad Hossein Sarrafzadeh

Mr. Habibollah Ramezanzade

by:

Kaveh Yazdifard

Presented on:

1385/10/3

Contents

Acknowledgement

Introduction

Shikimic Acid & its Natural Properties

Derivatives of Shikimic Acid

Avian Flu Sickness, Medications

Oseltamivir and Shikimic Acid's Role in Synthesis

Production of Shikimic Acid

Extracting Shikimic Acid from the Plant

Chemical Synthesis of Shikimic Acid

Biosynthesis & Shikimic Acid Pathway

Fermentation of Shikimic Acid using Microorganisms

Contrasting Production Methods & Advantages of Fermentative method

Investigating Appropriate Strains

Results & Future Aspects of Shikimic Acid Fermentation

References

Acknowledgement

The achieved results in this seminar and the upcoming relevant project are owing to undeniable helps and support of Zakaria Pharmaceutical Co.'s CEO Mr. Ramezanzadeh & my colleagues in R&D sector, mainly the R&D director Dr. Jassouri.

In clarifying my viewpoints on the project and on making a better literature work for the present seminar I strongly benefited from the helps of Dr. Sarrafzadeh and Dr. Yegani, to whom I shall always be grateful.

Introduction

The present seminar is a brief overview of the theoretical studies, toward implementing the industrial bioproduction plant in Zakaria Pharmaceuticals Co. The whole executive results will soon be handed over as the fellow student's MSc. Project.

Shikimic Acid & its Natural Properties

(3R, 4S, 5R)- (−)-3, 4, 5-Trihydroxy-1-cyclohexenecarboxylic acid

Shikimic acid, more commonly known as its anionic form shikimate, is an important biochemical intermediate in plants and microorganisms. Its name comes from the Japanese flower shikimi (Illicium anisatum), from which it was first isolated.

Shikimic acid is a hydroaromatic intermediate in the common pathway of aromatic amino acid biosynthesis. Although the common pathway has been observed in plants, microbes, and parasites, this wide distribution does not translate into abundant availability of the pathway's biosynthetic intermediates such as shikimic acid. A tedious, multistep process is used for isolation of shikimic acid from Illicium spp., a plant whose cultivation has never benefited from large-scale monoculture.

It is an attractive chiral synthon with its highly functionalized; six-membered carbocyclic ring and, multiple asymmetric centers.

Shikimic acid plays a key role in the biosynthesis of many important natural products including aromatic amino acids, alkaloids, phenolics, and phenylpropanoids. It plays such an important role that one of the key biosynthetic pathways is referred to as the shikimate pathway.

Shikimic acid

Chemical name

(3R,4S,5R)-3,4,5-Trihydroxy-

1-cyclohexenecarboxylic acid

Chemical formula

C7H10O5

Molecular mass

174.15 g/mol

Melting point

185-187 oC

CAS number

[138-59-0]

EINECS number

205-334-2

Derivatives of Shikimic Acid

The carbocyclic array of chirality displayed by shikimic acid has attracted attention as the scaffold for synthesis of a large combinatorial library. However, synthetic utilization of shikimic acid has been much more restricted in comparison to the more abundantly available and less expensive quinic acid.

Amino acids are today of considerable commercial importance, and are used in a wide range of applications, from additives in food to raw material in the pharmaceutical industry. Many of the amino acids are produced in large quantities.

Chiral as well as aromatic chemicals can also be synthesized from shikimic acid.

The utility of shikimic acid in chemical synthesis is reflected in its use as the starting material for the manufacture of Tamiflu, an orally effective anti-influenza agent. More recently, reaction of shikimic acid in near-critical water was observed to produce phenol, thereby establishing a route for the synthesis of this large volume commodity chemical from renewable feedstocks. Microbe-catalyzed synthesis of shikimic acid from inexpensive glucose derived