<PAGE>


       CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED
       AND FILED SEPARATELY WITH THE COMMISSION. CONFIDENTIAL TREATMENT
       HAS BEEN REQUESTED WITH RESPECT TO THE OMITTED PORTIONS.

                                                                  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 [**] to be conducted over the [**], and an [**]
to be conducted over the [**], 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 [**] 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.



[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT
TO THE OMITTED PORTIONS.

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2. In accordance with the terms of the AGREEMENT, for Year 2 of the RESEARCH
PROGRAM, RWJPRI shall fund [**] on the [**]. RWJPRI acknowledges that [**]
already been provided in Year 1 with payment therefor deferred until Year 2.
Thus, RWJPRI shall provide funding for [**] for the combined programs for
Year 2 in accordance with the terms of the AGREEMENT.

3. [**] shall be deemed an [**] and RWJPRI has made the $[**] ([**] Dollar)
payment due under Section 6.2.1. [**] 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
   -----------------------------------------

Name: DANIEL V. SANT
     ---------------------------------------

Title:   Chief Executive

Date:    17 MARCH 2000
     ---------------------------------------


For and on Behalf of THE R.W. JOHNSON PHARMACEUTICAL RESEARCH INSTITUTE

By:      /s/ P.A. Peterson
   -----------------------------------------

Name: P.A. PETERSON, MD, PhD
     ---------------------------------------

Title:   President

Date:    MARCH 17, 2000
     ---------------------------------------



[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT
TO THE OMITTED PORTIONS.