Scope and limitations of chemical and biochemical methods are generally described. Chemical methods can be widely used for the preparation of various and abundant compounds, for instance by using high temperature, high pressure, strong bases and the elements such as rhodium and palladium which are not utilized by living things.
On the contrary, biochemical methods are chiefly used for the preparation of optically active compounds, by using enzymes which catalyze the asymmetric reactions under mild conditions.
As an example, chemical and biochemical preparations of DL- and D (L) -α-hydroxyacids from aldehydes or esters by one carbon homologation are comparatively stated.

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Recent application of microbial transformation to acyclic hydrophobic compounds such as n-alkane, linear terpenoids and fatty acids are reviewed with emphasis on Coryneform bacteria which were isolated from soil using squalene as carbon source.

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New steroid fermentation processes that produce a variety of intermediates from sterols such as cholesterol and phytosterols have recently been developed.
Especially, two fermentation processes for producing intermediates ADD and 4 AD, respectively, have been put into practice for the production of sex hormones and a diuretic drug, spironolactone. New techniques that consist of fermentation processes and the succeeding chemical syntheses are replacing the conventional processes using diosgenin as the starting material.
The microbial processes have been accomplished by the isolation of mutants whose metabolic pathway in cholesterol degradation have been blocked by the enzyme deletions that have resulted in the accumulation of a large amount of required intermediates, on the basis of the establishment of the preceding ADD fermentation techniques using chelating agents as inhibitors. Furthermore, for the production of corticoids which are a majority of steroid hormones, some microorganisms supplying useful steroid intermediates have been isolated and some new production routes are now being available.

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Recently, organic syntheses are directed toward very complex compounds and hence the development of highly selective reactions is required. Thus, it becomes increasingly important to utilize enzymatic reactions as key steps in organic synthesis. This article reviews the recent topics in microbial and enzymatic oxidations of organic compounds and their application to the synthesis of physiologically active compounds. The application of the biological systems are classified into types of reactions including, a) oxidation of saturated C-H bonds, b) oxidation of unsaturated bonds, c) oxidation of alcohols, d) oxidation of sulfides. Emphasis is placed to the chemo-, regio-, and stereo-selectivities of the reactions. Reductive reactions containing C-C bond formations are also described briefly.

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Asymmetric reduction of α-methyl β-keto ester and β-methyl α-keto ester by means of yeasts was carried out. Both keto esters were found to be reduced by a variety of yeasts to give optically active hydroxy esters having two chiral centers. The absolute configuration and the optical purity of the reduction products were primarily determined by measuring the 400 MHz NMR spectra of the (+) -MTPA esters of the alcohols produced.
The successful use of the chiral synthons prepared by the present method in high optical purity to the synthesis of (-) -oudemansin is described.

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Recent examples in the applications of biochemical systems in the syntheses of natural products are reviewed with special emphasis on the enantioselectivities of biochemical reactions.

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By selected microorganisms (±) - cyclic terpenealcohols (menthols, carvomenthols, isopulegols, carveols and borneols) were resolved via asymmetric hydrolysis of the corresponding acetates and chloroacetates at the high concentrations (110 %) of racemic substrates. Generally, the acetates of (1 R) -2, 5- disubstituted 1- cyclohexanols were hydrolyzed faster than those of their enantiomeric (1 S) - alcohols. On the contrary, the acetates of (1 S) -sec- acyclic alcohols faster than those of their enantiomeric (1 R) - alcohols. Optical purities of separated alcohols were changed by microorganisms used and hydrolysis ratios. This microbial resolution was used effectively for syntheses of chiral building blocks for optically active carotenoids and cycloheximide antibiotic.

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Recent advances in the synthesis of optically active amino acids by enzymatic method are described. L-Lysine, L-cysteine, L-tryptophan and D-forms of various amino acids, including D-p-hydroxyphenylglycine, are synthesized from chemically synthesized substrates by asymmetric ringopening hydrolysis. Multifunctional pyridoxal enzymes are useful for synthesis of various aromatic amino acids and sulfur-containing amino acids. Several enzymatic reactions being useful for production of amino acids are also described.
The described enzymatic methods are simple and the most economical process to date for the industrial production of these amino acids.

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Synthesis of biologically interesting nucleosides by a combination of chemical and enzymatic reactions is reviewed. As a likely source of enzyme, Enterobacter aerogenes was selected and its nucleoside phosphorylases were found to catalyze a transglycosyl reaction between pentofuranose and purine or pyrimidine base at relatively high temperature of 60°C. Using this procedure, a variety of nucleoside analogs and nucleosidic antibiotics which have been shown to have antiviral or antitumor activity were synthesized. Noteworthy among them are adenine arabinoside, guanine arabinoside, 2'-amino-2'-deoxyadenosine, 2'-amino -2'-deoxyguanosine and Virazole. It is of special interest that adenine arabinoside can be produced in a good yield with ease and on a large scale. Furthermore, it is reported that the methodology also serves for the preparation of new biologically interesting nucleosides.

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This review deals with the coimmobilization methods of coenzyme and enzymes and their application to continuous production of various materials in enzyme reactors. The methods are divided into four major groups according to the used form of coenzyme : water-soluble polymer-bound form, water-insoluble polymer-bound form, covalently enzyme-bound form, and native form. Each case is further divided into groups based on the practical use, system, or apparatus in view of how to use the coenzyme together with the enzymes. Typical examples are cited in some detail and their merits and demerits are discussed. Synthetic methods of polymer-bound coenzyme and regeneration system of coenzymes are also summarized.

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Technology for a continuous ethanol fermentation process was developed by means of immobilized living cells using yeast cells and specially designed artificial resins.
Yeast which has the ability to produce ethanol was screened from Saccharomyces genus and mixed with prepolymers of photocrosslinkable resin, then illuminated with an active ray (for example, chemical lamp) to change the prepolymers into three dimensional cross-linked polymers in which yeast was entrapped. Immobilized yeast processed into appropriate thinner sheet was packed in a fermentor and a diluted molasses solution fed to the fermentor. The fermentation temperature was kept at about 30-32°C and the pH at 4-5.
As a result of a bench scale test (10 litres of ethanol a day) and pilot plant test (250 litres of ethanol a day), the constant activity of the yeast and high ethanol yield on sugar during long-term operation was confirmed and it was also established that the ethanol productivity was several times that of conventional suspended state batch system fermentation.

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