EXHIBIT 10.12



             AMENDMENT NUMBER 1 TO RESEARCH AND LICENSE AGREEMENT BY
                 AND BETWEEN KOSAN BIOSCIENCES AND R.W. JOHNSON
                        PHARMACEUTICAL RESEARCH INSTITUTE

This Amendment dated MAR 17, 2000 is made to the RESEARCH AND LICENSE AGREEMENT
(hereinafter called the "AGREEMENT"), made as of September 28, 1998 by and
between KOSAN BIOSCIENCES, INC., a corporation organized under California law
having its principal office at 3832 Bay Center Place, Hayward, California 94545
(hereinafter called "KOSAN");

         ON THE ONE HAND, AND:

         ORTHO MCNEIL PHARMACEUTICAL, INCORPORATED (hereinafter called
"ORTHO"), a company organized under Delaware law, having its principal office at
U.S. Route 202, Raritan, New Jersey 08869; and

         the R.W. JOHNSON PHARMACEUTICAL RESEARCH INSTITUTE (hereinafter called
"RWJPRI"), a division of Ortho McNeil Pharmaceutical, Incorporated, having its
principal office at U.S. Route 202, Raritan, New Jersey 08869 (ORTHO and RWJPRI
hereinafter collectively called "LICENSEE")

                                                              ON THE OTHER HAND,

WITNESSETH:

         A. WHEREAS, KOSAN and LICENSEE have entered into the AGREEMENT
providing for a collaborative research drug discovery program as generally
described in the RESEARCH PLAN attached thereto as Appendix A;

         B. WHEREAS, the RESEARCH PLAN provided for two projects to be conducted
by the parties, a Fast Track Project to be conducted over the first twelve
months, and an SAR Project to be conducted over the first twenty-four months,
each with a provision for additional CONTINGENT WORK, to be performed in the
event a GO DECISION was made for the Project;

         C. WHEREAS, having completed the first twelve months of the RESEARCH
PROGRAM, the parties wish to fund the CONTINGENT WORK on the Fast Track PROJECT
and to reserve the rights to RWJ-351055 under provisions of the AGREEMENT:

         NOW, THEREFORE, in consideration of the premises and the performance of
covenants herein contained, the parties agree to amend the AGREEMENT as follows:

1. Unless otherwise defined herein, all capitalized terms used herein shall have
the same meaning as set forth in the AGREEMENT.



2. In accordance with the terms of the AGREEMENT, for Year 2 of the RESEARCH
PROGRAM, RWJPRI shall fund 4 FTE's for the CONTINGENT WORK on the Fast Track
Project and 12 FTE's for the SAR PROJECT. RWJPRI acknowledges that one of the 4
FTE's has already been provided in Year 1 with payment therefor deferred until
Year 2. Thus, RWJPRI shall provide funding for 16 FTE's for the combined
programs for Year 2 in accordance with the terms of the AGREEMENT.

3. RWJ-351055 shall be deemed an FTE and RWJPRI has made the $250,000 (Two
Hundred Fifty Thousand Dollar) payment due under Section 6.2.1. RWJ-351055 shall
be a reserved Compound under the provisions Section 3.5.6 until such time as it
is designated a Licensed Compound under the Agreement or the end of the
NON-EXCLUSIVE SCREENING PERIOD, whichever shall first occur.
4. Except as amended herein, all of the terms and conditions of the AGREEMENT
shall remain in full force and effect.

         IN WITNESS WHEREOF, the parties hereto have hereunto set their hands
and duly executed this Amendment AGREEMENT on the date(s) indicated below, to be
effective the day and year first above written.

For and on Behalf of KOSAN BIOSCIENCES, INC.

By:      /s/ Daniel V. Sant
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Name: DANIEL V. SANT
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Title:   Chief Executive

Date:    17 MARCH 2000
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For and on Behalf of THE R.W. JOHNSON PHARMACEUTICAL RESEARCH INSTITUTE

By:      /s/ P.A. Peterson
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Name: P.A. PETERSON, MD, PhD
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Title:   President

Date:    17 MARCH 2000
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